Edward L Peterson

Henry Ford Health System, Detroit, Michigan, United States

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Publications (216)1374.64 Total impact

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    ABSTRACT: Levels of the chemokine fractalkine (FKN) are increased in patients with chronic heart failure (HF) and our studies show that aged mice lacking the prostaglandin E2 EP4 receptor subtype (EP4-KO) have increased cardiac FKN with a phenotype of dilated cardiomyopathy. However, how FKN participates in the pathogenesis of heart failure has rarely been studied. We therefore hypothesized that FKN contributes to the pathogenesis of heart failure and anti-FKN treatment prevents heart failure induced by myocardial infarction (MI) more effectively in EP4-KO mice. Male EP4-KO mice and wild type littermates underwent sham or MI surgery and were treated with an anti-FKN antibody or control IgG. At 2 wks post MI, echocardiography was performed and hearts excised for infarct size determination, immunohistochemistry and Western blot of signaling molecules. Since FKN protein levels in the left ventricle were increased similarly in both strains after MI and anti-FKN treatment improved survival and cardiac function in both strains; we subsequently used only WT mice to examine the mechanisms whereby anti-FKN is cardioprotective. Myocyte cross-sectional area (MCSA) and interstitial collagen fraction (ICF) were reduced after anti-FKN treatment, as were macrophage migration and gelatinase activity. Finally, activation of ERK 1/2 and p38MAPK were reduced after neutralization of FKN. In vitro, FKN increased fibroblast proliferation. In conclusion, increased FKN contributes to heart failure after MI. This effect is not exacerbated in EP4-KO mice, suggesting no link between FKN and lack of EP4. Overall, inhibition of FKN may be important to preserve cardiac function post MI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Experimental physiology 05/2015; DOI:10.1113/EP085104 · 2.87 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis and end organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e. Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 weeks had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5 and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1 and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    American journal of physiology. Renal physiology 03/2015; DOI:10.1152/ajprenal.00039.2015 · 3.30 Impact Factor
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    ABSTRACT: Afferent (Af-Art) and efferent arterioles (Ef-Art) resistance regulate glomerular capillary pressure (GCP). The nephron regulates Af-Art resistance via: 1) vasoconstrictor tubuloglomerular feedback (TGF), initiated in the macula densa via Na/K/2Cl cotransporters (NKCC2); and 2) vasodilator connecting tubuloglomerular feedback (CTGF), initiated in connecting tubules (CT) via epithelial Na channels (ENaC). Furosemide inhibits NKCC2 and TGF. Benzamil inhibits ENaC and CTGF. In vitro, CTGF dilates preconstricted Af-Arts. In vivo, benzamil decreases stop-flow pressure (PSF), suggesting that CTGF antagonizes TGF; however, even when TGF is blocked, CTGF does not increase PSF, suggesting there is another mechanism antagonizing CTGF. We hypothesize that in addition to NKCC2, activation of Na/H exchanger (NHE) antagonizes CTGF, and when both are blocked CTGF dilates Af-Arts and this effect is blocked by a CTGF inhibitor benzamil. Using micropuncture, we studied the effects of transport inhibitors on TGF responses by measuring PSF while increasing nephron perfusion from 0 to 40 nL/min. Control TGF response (-7.9±0.2 mmHg) was blocked by furosemide (-0.4±0.2 mm Hg; P<0.001). Benzamil restored TGF in the presence of furosemide (furosemide: -0.2±0.1 vs furosemide+benzamil: -4.3±0.3 mmHg, P<0.001). With furosemide and NHE inhibitor, dimethylamiloride (DMA), increase in tubular flow increased PSF (furosemide+DMA: 2.7±0.5 mmHg, n=6), and benzamil blocked this (furosemide+DMA+benzamil: -1.1±0.2 mmHg, P<0.01, n=6). We conclude that NHE in the nephron decreases PSF (Af-Art constriction) when NKCC2 and ENaC are inhibited, suggesting that in the absence of NKCC2, NHE causes a TGF response and that CTGF dilates the Af-Art when TGF is blocked with NKCC2 and NHE inhibitors. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    American journal of physiology. Renal physiology 02/2015; 308(9):ajprenal.00605.2014. DOI:10.1152/ajprenal.00605.2014 · 3.30 Impact Factor
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors (GLP-1 agents) may be protective in heart failure (HF). We set out to determine whether GLP-1 agent use is associated with HF risk in diabetics. Retrospective cohort study of members of a large health system. We identified >19,000 adult diabetics from January 1, 2000-July 1, 2012. GLP-1 agent users were matched 1:2 to controls using propensity matching based on age, race, gender, coronary disease, HF, diabetes duration, and number of anti-diabetic medications. The association of GLP-1 agents with time to HF hospitalization was tested with multivariable Cox regression. All-cause hospitalization and mortality were secondary endpoints. We identified 1,426 users of GLP-1 agents and 2,798 controls. Both were similar except for angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEi/ARB) use, number of anti-diabetic medications and age. There were 199 hospitalizations, of which 128 were for HF, and 114 deaths. GLP-1 agents were associated with reduced risk of HF hospitalization (adjusted hazard ratio [aHR] 0.51; 95% confidence interval [CI] 0.34-0.77, p=0.002), all-cause hospitalization (aHR 0.54; 95% CI 0.38-0.74, p=0.001), and death (aHR 0.31; 95% CI 0.18-0.53, p=0.001). GLP-1 agents may reduce the risk of HF events in diabetics. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of Cardiac Failure 10/2014; DOI:10.1016/j.cardfail.2014.10.012 · 3.07 Impact Factor
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    ABSTRACT: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II).
    Journal of Hypertension 10/2014; 33(1). DOI:10.1097/HJH.0000000000000358 · 4.22 Impact Factor
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    ABSTRACT: Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration.
    Prostaglandins & other lipid mediators 09/2014; 113. DOI:10.1016/j.prostaglandins.2014.09.002 · 2.86 Impact Factor
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    ABSTRACT: Thymosin β4 (Tβ4) promotes cell survival, angiogenesis, tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg/kg/day i.p. via osmotic minipump) for 7 days or 5 weeks. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis and interstitial collagen fraction (ICF) histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of intercellular adhesion molecule-1 (ICAM-1) and p53 by immunoblot. Tβ4 reduced cardiac rupture that was associated with decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, decrease in gelatinolytic activity and ICAM-1 and p53 expression, as well as the increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, and markedly reduced ICF and increased capillary density. In murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.
    AJP Heart and Circulatory Physiology 07/2014; 307(5). DOI:10.1152/ajpheart.00129.2014 · 4.01 Impact Factor
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    ABSTRACT: The afferent arteriole (Af-Art) controls glomerular capillary pressure, an important determinant of glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (-3.1±0.8 vs. 0.5±0.8 µm, P<0.01). The 20-HETE antagonist 20-HEDE (10(-6)M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10-6M). Maximum ATP-induced constriction was attenuated in Dahl SS compared to Dahl SR (1.5±0.5 vs. 7.4±0.8 µm, P<0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.
    American journal of physiology. Renal physiology 07/2014; 307(5). DOI:10.1152/ajprenal.00283.2014 · 3.30 Impact Factor
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    ABSTRACT: Infection is the second leading cause of death in hemodialysis patients. Catheter-related bloodstream infection and infection-related mortality have not improved in this population over the past two decades. This study evaluated the impact of a prophylactic antibiotic lock solution on the incidence of catheter-related bloodstream infection and mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective, multicenter, observational cohort study compared the effectiveness of two catheter locking solutions (gentamicin/citrate versus heparin) in 555 hemodialysis patients dialyzing with a tunneled cuffed catheter between 2008 and 2011. The groups were not mutually exclusive. Rates of catheter-related bloodstream infection and mortality hazards were compared between groups.RESULTS: The study population (n=555 and 1350 catheters) had a median age of 62 years (interquartile range=41-83 years), with 50% men and 71% black. There were 427 patients evaluable in the heparin period (84,326 days) and 322 patients evaluable in the antibiotic lock period (71,192 days). Catheter-related bloodstream infection in the antibiotic lock period (0.45/1000 catheter days) was 73% lower than the heparin period (1.68/1000 catheter days; P=0.001). Antibiotic lock use was associated with a decreased risk of catheter-related bloodstream infection compared with heparin (risk ratio, 0.23; 95% confidence interval, 0.13 to 0.38 after multivariate adjustment). Cox proportional hazards modeling found that antibiotic lock was associated with a reduction in mortality (hazard ratio, 0.36; 95% confidence interval, 0.22 to 0.58 in unadjusted analyses; hazard ratio, 0.32; 95% confidence interval, 0.14 to 0.75 after multivariate adjustment). The rate of gentamicin-resistant organisms decreased (0.40/1000 person-years to 0.22/1000 person-years) in the antibiotic lock period (P=0.01).CONCLUSIONS: The results of this study show that the use of a prophylactic, gentamicin/citrate lock was associated with a substantial reduction in catheter-related bloodstream infection and is the first to report a survival advantage of antibiotic lock in a population at high risk of infection-related morbidity and mortality.
    Clinical Journal of the American Society of Nephrology 06/2014; 9(7). DOI:10.2215/CJN.11291113 · 5.25 Impact Factor
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    ABSTRACT: Increasing Na delivery to epithelial Na channels (ENaC) in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone sensitizes CTGF via a nongenomic mechanism that stimulates CNT ENaC via the aldosterone receptor GPR30. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. During the control period, the concentration of NaCl that elicited a half-maximal response (EC50) was 37.0±2.0 mmol/L; addition of aldosterone 10-8 mol/L to the CNT lumen caused a left-shift (decrease) in EC50 to 19.3±1.3 mmol/L (P=0.001 vs. Control; n=6). Neither the transcription inhibitor actinomycin D (control EC50=34.7±1.9 mmol/L; aldosterone+actinomycin D EC50=22.6±1.6 mmol/L; n=6; P < 0.001) nor the translation inhibitor cycloheximide (control EC50=32.4±4.3 mmol/L; aldosterone+cycloheximide EC50=17.4±3.3 mmol/L; n=6; P < 0.001) prevented the effect of aldosterone. The aldosterone antagonist eplerenone prevented the sensitization of CTGF by aldosterone (control EC50=33.2±1.7 mmol/L; aldosterone+eplerenone EC50=33.5±1.3 mmol/L; n=7). The GPR30 receptor blocker G-36 blocked the sensitization of CTGF by aldosterone (aldosterone EC50=16.5±1.9 mmol/L; aldosterone+G-36 EC50=29.0±2.1 mmol/L; n=7; P < 0.001). Finally, we found that the sensitization of CTGF by aldosterone was mediated, at least in part, by the sodium/hydrogen exchanger (NHE). We conclude that aldosterone in the CNT lumen sensitizes CTGF via a nongenomic effect involving GPR30 receptors and NHE. Sensitized CTGF induced by aldosterone may contribute to renal damage by increasing Af-Art dilation and glomerular capillary pressure (glomerular barotrauma).
    American journal of physiology. Renal physiology 06/2014; 307(4). DOI:10.1152/ajprenal.00072.2014 · 3.30 Impact Factor
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    ABSTRACT: Context: Metformin is considered first-line treatment for type 2 diabetes mellitus. However, little is known about its effects in African American individuals. Objective: The objective of the study was to assess whether metformin's effect on glycemic control differs by race-ethnicity Design: Electronic health records were used to identify adults who had a diagnosis of diabetes, two or more fills of metformin, and two or more glycated hemoglobin (HbA1c) measurements. Pharmacy claims were used to estimate metformin exposure based on fill frequency and dose dispensed. Regression analyses modeled the relationship between metformin exposure and HbA1c levels. Analyses were stratified by race-ethnicity and baseline HbA1c values. Setting: The study was conducted at a large health system in southeast Michigan. Main Outcome Measure: Differences in HbA1c levels while on metformin were measured. Results: We identified 19ü672 patients with diabetes taking metformin; 7429 were African American and 8783 were European American. Baseline HbA1c values in these two groups were 7.81% (61.8 mmol/mol) and 7.38% (57.1 mmol/mol), respectively. Compared with no use, metformin was associated with a 0.62% (6.8 mmol/mol) reduction in HbA1c; however, there was a significant difference by race-ethnicity (P < .001). Among African American individuals, metformin use was associated with a 0.90% (9.8 mmol/mol) reduction in HbA1c levels, whereas among European Americans, metformin was associated with a 0.42% (4.6 mmol/mol) reduction. Irrespective of baseline HbA1c, metformin use was associated with lower HbA1c levels in African American individuals. Conclusions: African American individuals appear to have a better glycemic response to metformin when compared with European Americans. Further studies are needed to determine whether this translates to commensurate reductions in diabetes complications.
    Journal of Clinical Endocrinology &amp Metabolism 06/2014; 99(9):jc20141539. DOI:10.1210/jc.2014-1539 · 6.31 Impact Factor
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    ABSTRACT: Purpose: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been established as a mainstay of heart failure treatment. Current data are limited and conflicting regarding the consistency of ACE/ARB benefit across race groups in heart failure. This study aims to clarify this point. Methods: This was a retrospective study of insured patients with a documented ejection fraction of less than 50%, hospitalized for heart failure between January 2000 and June 2008. Pharmacy claims data were used to estimate ACE/ARB exposure over 6-month rolling windows. The association between ACE/ARB exposure and all-cause hospitalization or death was assessed by proportional hazards regression, with adjustment for baseline covariates and [beta]-blocker exposure. Further analyses were stratified by race, and included an ACE/ARB x Race interaction term. Results: A total of 1095 patients met inclusion criteria (619 African-American individuals). Median follow-up was 2.1 years. In adjusted models, ACE/ARB exposure was associated with lower risk of death or hospitalization in both groups (African-Americans hazard ratio 0.47, P < 0.001; whites hazard ratio 0.55, P < 0.001). A formal test for interaction was consistent with similar effects in each group (P = 0.861, [beta] = 0.04). Conclusion: ACE/ARB exposure was equally associated with a protective effect in preventing death or rehospitalization among heart failure patients with systolic dysfunction in both African-American patients and whites. Copyright
    Journal of Cardiovascular Medicine 05/2014; DOI:10.2459/JCM.0000000000000091 · 1.41 Impact Factor
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    ABSTRACT: Rising prescription opioid use and abuse have prompted widespread concern. However, to date there have been few rigorous investigations into the policies and events which may have contributed to these trends.
    Pain physician 05/2014; 17(3):205-16. · 4.77 Impact Factor
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    ABSTRACT: The activation of angiotensin II type 2 receptor (AT2R) has been considered cardioprotective. However, there are controversial findings regarding the role of overexpressing AT2R in the heart. Using transgenic mice with different levels of AT2R gene overexpression in the heart (1, 4, or 9 copies of the AT2R transgene: Tg(1), Tg(4), or Tg(9)), we studied the effect of AT2R overexpression on left ventricular remodeling and dysfunction post-myocardial infarction (MI). Tg(1), Tg(4), Tg(9), and their wild-type littermates were divided into (1) sham MI, (2) MI plus vehicle, and (3) MI plus AT2R antagonist. Treatments were started 4 weeks after MI and continued for 8 weeks. AT2R protein and mRNA expression in the heart was significantly increased in transgenic mice, and the increase positively correlated with copies of the transgene. AT1R protein and mRNA expression remained unchanged in Tg(1) and Tg(4) but slightly increased in Tg(9) mice. Systolic blood pressure and cardiac phenotypes did not differ among strains under basal conditions. MI caused myocardial hypertrophy, interstitial fibrosis, ventricular dilatation, and dysfunction associated with increased protein expression of Nox2 and transforming growth factor β1. These pathological responses were diminished in Tg(1) and Tg(4) mice. Moreover, the protective effects of AT2R were abolished by AT2R antagonist and also absent in Tg(9) mice. We thus conclude that whether overexpression of AT2R is beneficial or detrimental to the heart is largely dependent on expression levels and possibly via regulations of Nox2 and transforming growth factor β1 signaling pathways.
    Hypertension 04/2014; 63(6). DOI:10.1161/HYPERTENSIONAHA.114.03247 · 7.63 Impact Factor
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    ABSTRACT: Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E2 EP4 receptor sub-type (EP4 KO) exhibit reduced cardiac function. Gene array on left ventricles (LV) showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE2 and contributes to depressed contractility via alterations in intracellular calcium. Fractalkine was measured in LV of 28-32 week old male EP4 KO and wild type controls (WT) by ELISA and the effect of PGE2 on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM) from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso) stimulation. LV fractalkine was increased in EP4 KO mice but surprisingly, PGE2 regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+) transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery. Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium.
    PLoS ONE 09/2013; 8(7):e69832. DOI:10.1371/journal.pone.0069832 · 3.53 Impact Factor
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    ABSTRACT: Nonadherence to inhaled corticosteroids (ICSs) for asthma maintenance therapy is common and is associated with poor asthma outcomes. Simplifying dosing regimens for some chronic disease conditions has resulted in better adherence; however, little is known regarding the effect of ICS dosing on adherence for the treatment of asthma. To determine whether once daily dosing is associated with higher adherence to ICS therapy when compared with 2 or more times daily dosing among patients with asthma. Six years of pharmacy claims data were linked with prescription information to estimate ICS therapy adherence for patients with asthma 12 to 56 years of age who were members of a large health maintenance organization. Patient follow-up continued from the initial ICS fill until one of the following: the last ICS fill in the observation period, a switch of ICS dosing regimen, or the initiation of ICS and long-acting β-agonist combination therapy. Adherence was estimated by calculating a continuous multiple-interval measure of medication availability. Regression models were used to assess the relationship between adherence in patients treated with once daily vs 2 or more times daily ICS therapy. Among the 1,302 patients who met the inclusion criteria, 17% were prescribed once daily therapy, and 83% were prescribed 2 or more times daily therapy. Models comparing ICS adherence among individuals following once daily and 2 or more times daily ICS regimens suggested that once daily dosing was associated with an approximately 20% increase in adherence. This significant difference persisted among subgroups defined by sex, race/ethnicity, age, and asthma severity. Once daily dosing was associated with higher adherence to ICS therapy; this included clinically relevant subgroups.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/2013; 111(3):216-20. DOI:10.1016/j.anai.2013.06.008 · 2.75 Impact Factor
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    ABSTRACT: Retention of study participants in randomized controlled trials (RCTs) is crucial to study validity. We analyzed the results of four retention strategies used to reconnect with urban teens enrolled in a school-based RCT and overdue for a 12-month follow-up survey. Traditional retention strategies used to reconnect with teens categorized as 'unable to contact' were weekly redials of nonworking telephone numbers and mailings to the student's home. Nontraditional retention strategies were obtaining assistance from school administration and performing outreach on Facebook. Of the 422 students enrolled, 125 (29.5%) were overdue for a 12-month follow-up survey, but had no working telephone number (unable to contact). We made 196 attempts to contact these 125 students, of which 82 attempts (41.8%) were successful in 'reconnecting' with the student. Using 'mailed reminder letters' as the referent category, odds ratios (95% confidence intervals) for the association between the strategy used and reconnecting were 4.60 (1.8-11.8), 1.94 (1.01-3.73), and 2.91 (0.58-14.50), respectively, for telephone number redials, Facebook outreach, and school administration assistance. Of the 422 students, 380 (90%) ultimately completed the 12-month follow-up survey. Retention strategies were not applied hierarchically or systematically. We were unable to determine student preference for a particular strategy. Findings are likely only applicable to similar study populations. A mix of traditional retention strategies and more contemporary methods was effective in reconnecting with urban teenagers enrolled in a school-based RCT and in controlling attrition during the 12-month follow-up survey period.
    Clinical Trials 08/2013; DOI:10.1177/1740774513498320 · 1.94 Impact Factor
  • Journal of Cardiac Failure 08/2013; 19(8):S30-S31. DOI:10.1016/j.cardfail.2013.06.102 · 3.07 Impact Factor
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    ABSTRACT: Myocardial matrix turnover involves a dynamic balance between collagen synthesis and degradation, which is regulated by matrix metalloproteinases (MMPs). N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) is a small peptide that inhibits cardiac inflammation and fibrosis. However, its role in MMP regulation is not known. Thus, we hypothesized that Ac-SDKP promotes MMP activation in cardiac fibroblasts and decreases collagen deposition via this mechanism. To that end, we tested the effects of Ac-SDKP on interleukin-1β (IL-1β; 5 ng/ml)-stimulated adult rat cardiac fibroblasts. We measured total collagenase activity, MMP-2, MMP-9, and MMP-13 expressions, and activity along with their inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. In order to examine the effects of Ac-SDKP on the signaling pathway that controls MMP transcription, we also measured nuclear factor-κB (NFκB) and p42/44 mitogen-activated protein kinase (MAPK) activation. Ac-SDKP did not alter collagenase or gelatinase activity in cardiac fibroblasts under basal conditions, but blunted the IL-1β-induced increase in total collagenase activity. Similarly, Ac-SDKP normalized the IL-1β-mediated increase in MMP-2 and MMP-9 activities and MMP-13 expression. Inhibition of MMPs by Ac-SDKP was associated with increased TIMP-1 and TIMP-2 expressions. Collagen production was not affected by Ac-SDKP, IL-1β, or a combination of both agents. Ac-SDKP blocked IL-1β-induced p42/44 phosphorylation and NFκB activation in cardiac fibroblasts. We concluded that the Ac-SDKP-inhibited collagenase expression and activation was associated with increased expression of TIMP-1 and TIMP-2. These pharmacological effects of Ac-SDKP may be linked to the inhibition of MAPK and NFκB pathway.
    Pflügers Archiv - European Journal of Physiology 05/2013; 465(10). DOI:10.1007/s00424-013-1262-8 · 3.07 Impact Factor
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    Journal of the American College of Cardiology 03/2013; 61(10). DOI:10.1016/S0735-1097(13)60689-0 · 15.34 Impact Factor

Publication Stats

14k Citations
1,374.64 Total Impact Points


  • 1994–2015
    • Henry Ford Health System
      • Department of Psychiatry
      Detroit, Michigan, United States
  • 1989–2015
    • Henry Ford Hospital
      • • Hypertension and Vascular Research Division
      • • Department of Internal Medicine
      • • Surgery
      Detroit, Michigan, United States
  • 2000–2009
    • Georgia Health Sciences University
      • Department of Pediatrics
      Augusta, GA, United States
  • 2007
    • Cancer Research and Biostatistics
      Seattle, Washington, United States
  • 2006
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • University of Chicago
      • Department of Molecular Genetics & Cell Biology
      Chicago, Illinois, United States
  • 2002–2006
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States
    • Georgia College
      Атина, Georgia, United States
  • 1999–2006
    • Wayne State University
      • Department of Pediatrics
      Detroit, Michigan, United States
  • 2004
    • Harvard Medical School
      Boston, Massachusetts, United States