[show abstract][hide abstract] ABSTRACT: In this study, we report the comparative result of long-term clinical prognoses for patients with no-option critical limb ischemia (CLI) caused by arteriosclerosis obliterans, who are implanted with autologous bone marrow mononuclear cells (BMMNC; n=74) or G-CSF-mobilized (M)-PBMNC (n=111), as no information is available on how the two treatments compare in terms of long-term prognosis, such as survival or amputation. We performed pooled analysis using data from two previous cohort studies. All patients had disease of Fontaine classification III or IV. The endpoints were OS and amputation-free survival (AFS). After adjustment for history of dialysis and Fontaine classification, there was no significant difference between the two treatments with respect to OS (hazard ratio (HR)=1.49; 95% confidence interval (CI)=0.74-3.03, P=0.26) or AFS (HR=0.96; 95% CI=0.61-1.51, P=0.87). The negative prognostic factors affecting OS or AFS were the small number of CD34-positive cells collected, history of dialysis, Fontaine classification, male sex and older age. These results suggest that there was no significant difference in long-term prognosis between patients treated with BMMNC and those treated with M-PBMNC. The number of CD34-positive cells collected was an important prognostic factor for amputation and death.
Bone marrow transplantation 02/2011; 46(2):278-84. · 3.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients.
We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants.
HD patients with PAD (n = 26; 21.9 [13.6-33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5-17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29-25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40-0.74; p < 0.001).
These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.
[show abstract][hide abstract] ABSTRACT: Primary percutaneous coronary intervention (PCI) for ST-elevated myocardial infarction (STEMI) results in dramatically improved clinical outcomes when performed in a timely manner. Although guidelines for STEMI patients recommend PCI should be performed by experienced operators with acceptable PCI volume, cardiologists in a local area must perform primary PCI at their own hospitals. This study evaluated the effects of cardiologist experience on outcomes for STEMI patients in a local area in Japan.Between April 2007 and March 2010, 140 consecutive STEMI patients were admitted to our hospital and 121 of these patients received primary PCI. STEMI patients undergoing primary PCI were divided into two groups according to the operator's experience as a cardiologist. We retrospectively analyzed their clinical backgrounds, PCI findings, in-hospital outcomes, and drug administration at discharge.There were no significant differences in any clinical characteristics, angiographic findings, or PCI procedures between the two groups. Clinical outcomes of the two groups were similar, except for the length of hospital stay (21.1 ± 5.8 versus 15.5 ± 9.7; P = 0.0255). The frequency of administration of drugs such as β-blockers (59.1% versus 34.0%; P = 0.0086), aldosterone blockade (10.4% versus 25.5%; P = 0.0334), and nicorandil (76.1% versus 25.5%; P = < 0.0001) was different between the two groups.The clinical outcomes of STEMI patients in this study were satisfactory and almost equivalent when compared according to the experience of the attending cardiologist. The present findings suggest the important clinical implication that younger cardiologists who have experienced PCI procedures to a certain extent can safely perform primary PCI and contribute to better prognoses of STEMI patients.
International Heart Journal 01/2011; 52(3):127-30. · 1.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: The accumulation of senescent cells within tissues can potentially lead to biological dysfunction and manifestation of disease associated with ageing. The majority of senescent cells display a commonly altered secretome similar to a wound healing response (termed the senescence-associated secretory phenotype or SASP), which could have deleterious implications on the tissue microenvironment. However, senescent cells also appear to have a cell-type (or even cell-strain) exclusive senescent phenotype (CESP), an area of research that is underexplored. One such CESP is the pro-calcificatory phenotype recently reported in senescent vascular smooth muscle cells (VSMCs). Senescent VSMCs have been shown to overexpress genes and proteins (including RUNX-2, alkaline phosphatase (ALP), type I collagen and BMP-2) associated with osteoblasts, leading to partial osteoblastic transdifferentiation. As such, it has been suggested that senescent VSMCs contribute to cardiovascular dysfunction through induction of vascular calcification. This review discusses recent findings on VSMC senescence and their potential role in the pathophysiology of vascular calcification.
[show abstract][hide abstract] ABSTRACT: Erythropoietin (EPO) enhances re-endothelialization and anti-apoptotic action. Larger clinical studies to examine the effects of high-dose EPO are in progress in patients with acute myocardial infarction (AMI).
The aim of this multi-center pilot study was to investigate the effect of `low-dose EPO' (6,000 IU during percutaneous coronary intervention (PCI), 24 h and 48 h) in 35 patients with a first ST-elevated AMI undergoing PCI who was randomly assigned to EPO or placebo (saline) treatment. Neointimal volume, cardiac function and infarct size were examined in the acute phase and 6 months later (ClinicalTrials.gov identifier: NCT00423020). No significant regression in in-stent neointimal volume was observed, whereas left ventricular (LV) ejection fraction was significantly improved (49.2% to 55.7%, P=0.003) and LV end-systolic volume was decreased in the EPO group (47.7 ml to 39.0 ml, P=0.036). LV end-diastolic volume tended to be reduced from 90.2% to 84.5% (P=0.159), whereas in the control group it was inversely increased (91.7% to 93.7%, P=0.385). Infarction sizes were significantly reduced by 38.5% (P=0.003) but not in the control group (23.7%, P=0.051). Hemoglobin, peak creatine kinase values, and CD34(+)/CD133(+)/CD45(dim) endothelial progenitors showed no significant changes. No adverse events were observed during study periods.
This is a first study demonstrating that short-term `low-dose' EPO to PCI-treated AMI patients did not prevent neointimal hyperplasia but rather improved cardiac function and infarct size without any clinical adverse effects.
[show abstract][hide abstract] ABSTRACT: Experience of primary percutaneous coronary intervention (PCI) for young adults with acute myocardial infarction (AMI) due to sequelae of Kawasaki disease (KD) has been extremely limited. In the present report on three young adults (two males and one female; age 20-35 years) with AMI, we performed primary PCI and intravascular ultrasound imaging (IVUS). Case 1 underwent thrombectomy alone in the proximal left circumflex coronary artery, and subsequent IVUS depicted a large aneurysm with an asymmetrically intimal thickening and a residual thrombus in the culprit. Case 2 underwent balloon dilation with adjunctive intracoronary thrombolysis in the proximal left anterior descending coronary artery (LAD), and IVUS during follow-up coronary angiography (CAG) delineated a regressed giant aneurysm with a markedly intimal thickening in the culprit. Case 3, with past history highly suggesting KD, underwent balloon dilation in the proximal LAD, and follow-up CAG as well as IVUS revealed a neoaneurysmal formation in the culprit. In all of the patients, PCI was angiographically effective at the acute phase without complication. Follow-up CAG performed 3-6 months after the procedure revealed no restenosis in all three cases, but a new coronary aneurysm still remained in case 3. Although case 1 and case 2 had no obvious history of KD, the vessel wall morphology from IVUS closely resembled the coronary sequelae after KD, suggesting that they might have antecedent incomplete KD. These cases suggest that primary PCI against coronary sequelae of KD in young AMI patients might be safe and effective in the short term.
Heart and Vessels 11/2010; 26(1):117-24. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bioenergetic homeostasis is altered in heart failure and may play an important role in pathogenesis. p53 has been implicated in heart failure, and although its role in regulating tumorigenesis is well characterized, its activities on cellular metabolism are just beginning to be understood. We investigated the role of p53 and its transcriptional target gene TP53-induced glycolysis and apoptosis regulator (TIGAR) in myocardial energy metabolism under conditions simulating ischemia that can lead to heart failure. Expression of p53 and TIGAR was markedly upregulated after myocardial infarction, and apoptotic myocytes were decreased by 42% in p53-deficient mouse hearts compared with those in wild-type mice. To examine the effect of p53 on energy metabolism, cardiac myocytes were exposed to hypoxia. Hypoxia induced p53 and TIGAR expression in a p53-dependent manner. Knockdown of p53 or TIGAR increased glycolysis with elevated fructose-2,6-bisphosphate levels and reduced myocyte apoptosis. Hypoxic stress decreased phosphocreatine content and the mitochondrial membrane potential of myocytes without changes in ATP content, the effects of which were prevented by the knockdown of TIGAR. Inhibition of glycolysis by 2-deoxyglucose blocked these bioenergetic effects and TIGAR siRNA-mediated prevention of apoptosis, and, in contrast, overexpression of TIGAR reduced glucose utilization and increased apoptosis. Our data demonstrate that p53 and TIGAR inhibit glycolysis in hypoxic myocytes and that inhibition of glycolysis is closely involved in apoptosis, suggesting that p53 and TIGAR are significant mediators of cellular energy homeostasis and cell death under ischemic stress.
[show abstract][hide abstract] ABSTRACT: Klotho is a circulating protein, and Klotho deficiency disturbs endothelial integrity, but the molecular mechanism is not fully clarified. We report that vascular endothelium in Klotho-deficient mice showed hyperpermeability with increased apoptosis and down-regulation of vascular endothelial (VE)-cadherin because of an increase in VEGF-mediated internal calcium concentration ([Ca(2+)]i) influx and hyperactivation of Ca(2+)-dependent proteases. Immunohistochemical analysis, the pull-down assay using Klotho-fixed agarose, and FRET confocal imaging confirmed that Klotho protein binds directly to VEGF receptor 2 (VEGFR-2) and endothelial, transient-receptor potential canonical Ca(2+) channel 1 (TRPC-1) and strengthens the association to promote their cointernalization. An in vitro mutagenesis study revealed that the second hydrolase domain of Klotho interacts with sixth and seventh Ig domains of VEGFR-2 and the third extracellular loop of TRPC-1. In Klotho-deficient endothelial cells, VEGF-mediated internalization of the VEGFR-2/TRPC-1 complex was impaired, and surface TRPC-1 expression increased 2.2-fold; these effects were reversed by supplementation of Klotho protein. VEGF-mediated elevation of [Ca(2+)]i was sustained at higher levels in an extracellular Ca(2+)-dependent manner, and normalization of TRCP-1 expression restored the abnormal [Ca(2+)]i handling. These findings provide evidence that Klotho protein is associated with VEGFR-2/TRPC-1 in causing cointernalization, thus regulating TRPC-1-mediated Ca(2+) entry to maintain endothelial integrity.
Proceedings of the National Academy of Sciences 10/2010; 107(45):19308-13. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vascular calcification is an important risk factor for cardiovascular diseases. Here, we investigated a role of dedifferentiated vascular smooth muscle cells (VSMCs) in the atherosclerotic intimal calcification.
We prepared human cultured VSMCs in either redifferentiatiated or dedifferentiated state and analyzed the gene expressions of bone-calcification regulatory factors. Expression of bone morphogenetic protein-2 (BMP-2), a potent initiator for osteoblast differentiation, was significantly enhanced in dedifferentiated VSMCs. Furthermore, endogenous BMP-2 antagonists, such as noggin, chordin, and matrix gamma-carboxyglutamic acid protein, were all downregulated in the dedifferentiated VSMCs. Conditioned medium from dedifferentiated VSMCs, but not from redifferentiated VSMCs, stimulated the osteoblastic differentiation of the mesenchymal progenitor C2C12 cells, which was abolished by BMP-2 knockdown. In atherosclerotic intima from apolipoprotein (apo)E-deficient mice, αSM-actin-positive cells, presumably dedifferentiated VSMCs, expressed BMP-2. We generated BMP-2-transgenic mice using αSM-actin promoter and crossed them with apoE-deficient mice (BMP-2-transgenic/apoE-knockout). Significantly accelerated atherosclerotic intimal calcification was detected in BMP-2-transgenic/apoE-knockout mice, although serum lipid concentration and atherosclerotic plaque size were not different from those in apoE-knockout mice. Enhanced calcification appeared to be associated with the frequent emergence of osteoblast-like cells in atherosclerotic intima in BMP-2-transgenic/apoE-knockout mice.
Our findings collectively demonstrate an important role of dedifferentiated VSMCs in the pathophysiology of atherosclerotic calcification through activating paracrine BMP-2 osteogenic signals.
[show abstract][hide abstract] ABSTRACT: Members of the fibroblast growth factor (FGF) family have been clinically applied to the treatment of ischemic diseases because of their strong angiogenic actions. Although tissue ischemia is predominantly caused by atherosclerosis, the roles of endothelial FGF receptors (FGF-Rs) in atherosclerosis remain obscure. We generated endothelial cell (EC)-targeted constitutively active FGF-R2-overexpressing mice, using the Tie2 promoter (Tie2-FGF-R2-Tg), and crossed them with apolipoprotein E (ApoE)-deficient mice (ApoE-KO) to generate Tie2-FGF-R2-Tg/ApoE-deficient mice (Tie2-FGF-R2-Tg/ApoE-KO). After being fed a Western diet for 8 wk, the Tie2-FGF-R2-Tg/ApoE-KO demonstrated 2.0-fold greater atherosclerotic lesion area on the luminal surfaces of the aortas than the ApoE-KO (P < 0.01). The level of p21(Cip1) protein, a cell cycle inhibitor, in the FGF-R2-overexpressing EC was 2.5-fold greater than that in the wild-type (WT) EC at the baseline (P < 0.01). FGF-R2 overexpression in the EC resulted in increased expression of VCAM-1 and ICAM-1, acceleration of apoptosis, and decreased proliferative activity, all of which were normalized by small interfering RNA (siRNA)-mediated knockdown of p21(Cip1) (75% reduction in protein level, P < 0.01). Furthermore, the expression of PDGF-B and Egr-1, a PDGF/p21(Cip1)-inducible transcription factor, in the aortic endothelium of Tie2-FGF-R2-Tg/ApoE-KO was significantly greater than that in ApoE-KO. The proliferation of vascular smooth muscle cells in the aortic media of Tie2-FGF-R2-Tg/ApoE-KO was 2.0-fold higher than that in ApoE-KO (P < 0.01). Thus our study reveals that endothelial FGF-R2 signaling aggravates atherosclerosis by promoting p21(Cip1)-mediated EC dysfunction and cautions against the use of FGF for therapeutic angiogenesis in the setting of atherosclerosis.
[show abstract][hide abstract] ABSTRACT: Though restenosis after drug-eluting stent implantation is still observed, the factors affecting post-sirolimus-eluting stent restenosis (re-restenosis) have not been fully determined. We evaluated the long-term angiographic outcomes and examined background factors affecting re-restenosis. We enrolled 51 patients with 68 sirolimus-eluting stent (SES) restenosis lesions who underwent target lesion revascularization (TLR) and angiographic follow-up studies. Re-restenosis was observed in 29 of 68 restenosis lesions, and the rate was 42.6%. Study subjects were divided into two groups: a re-restenosis (Re-R) group (20 patients) with 29 lesions and a restenosis (R) group (31 patients) with 39 lesions with no re-restenosis. There were no differences in age, sex, coronary risk factors, past history, or medications between the two groups. Re-restenosis was observed more frequently in the right coronary artery (Re-R group vs. R group; 65.5 vs. 33.3%, P = 0.009). The incidence of stent fracture was higher in the Re-R group (Re-R group vs. R group; 48.3 vs. 12.8%, P = 0.003). QCA results showed that the initial lesion length at the time of first coronary intervention was significantly longer in the Re-R group (Re-R group vs. R group; 21.6 ± 3.37 vs. 12.6 ± 4.98 mm, P = 0.049). The rate of re-restenosis was 47.1% when treated with POBA alone, while it was 36.7% with SES treatment. In multivariate analysis, the initial lesion length at the time of first coronary intervention (odds ratio = 1.64, 95% CI 1.29-2.06, P < 0.001) and stent fracture (odds ratio = 12.42, 95% CI 1.89-81.4, P = 0.009) were independent predictors of re-restenosis. This study demonstrates that recurrent restenosis with SES treatment is associated with lesion length and stent fracture, a finding that is beneficial in the management of restenosis after SES implantation.
Heart and Vessels 10/2010; 26(2):168-75. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Prolonged pre-hospital time for acute myocardial infarction (AMI) is associated with decreased indication for primary percutaneous coronary intervention (PCI). However, the efficacy of primary PCI in AMI patients with prolonged pre-hospital time has not been fully investigated in Japan.
A total of 3010 consecutive AMI patients admitted to AMI-Kyoto Multi-Center Risk Study Group hospitals were retrospectively analyzed, and the clinical characteristics and in-hospital prognosis of these patients were reviewed. Patients with pre-hospital delay [elapsed time (ET)>12 h] had a lower frequency of Killip≥3 (9.3%) and less frequently received primary PCI (77.7%) compared with patients with ET≤12 h. In the ET>12 h group, older patients or patients with MI history tended to be complicated by heart failure. Primary PCI was performed for patients with ET>12 h, irrespective of the severity of heart failure [Killip 1 (78.7%) vs Killip≥2 (74.0%); p=0.3827]. On multivariate logistic regression analysis, age [odds ratio (OR) 1.053], MI history (OR 2.860), Killip≥2 (OR 10.235), and multi-vessels or left main coronary artery as culprit (OR 11.712) were significant independent positive predictors of in-hospital mortality for patients with ET>12 h. Practice of primary PCI was not a significant negative predictor for patients with ET>12 h (OR 0.812), but it was for patients with ET≤12 h (OR 0.425).
These findings indicate that patients with ET>12 h have a less severe condition and less frequently receive primary PCI compared with patients with ET≤12 h. Although primary PCI is often performed for these patients irrespective of the severity of heart failure, no preferable effect of primary PCI on the in-hospital mortality is demonstrated. In contrary, practice of primary PCI is a significant negative predictor of in-hospital mortality for patients with ET≤12 h.
Journal of Cardiology 09/2010; 56(2):204-10. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Predictors of in-hospital outcome after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) requiring mechanical support devices such as intra-aortic balloon pumping (IABP) and/or percutaneous cardiopulmonary support (PCPS) remain unclear.
Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings, results of primary PCI, and in-hospital prognosis were retrospectively compared between primary PCI-treated AMI patients requiring mechanical assist devices (with-IABP/PCPS patients, n=275) and those without (without-IABP/PCPS patients, n=1,510). The with-IABP/PCPS patients were more likely to have a larger number of diseased vessels, lower Thrombolysis In Myocardial Infarction (TIMI) grade in the infarct-related artery (IRA) before/after primary PCI, and a significantly higher in-hospital mortality rate than the without-IABP/PCPS patients. On multivariate analysis, the number of diseased vessels > or =2 or diseased left main trunk (LMT) at initial coronary angiography (CAG) was the independent positive predictor of the in-hospital mortality in the with-IABP/PCPS patients, not in the without-IABP/PCPS patients, whereas acquisition of TIMI 3 flow in the IRA immediately after primary PCI was the negative predictor in the without-IABP/PCPS patients, not in the with-IABP/PCPS patients.
The number of diseased vessels > or =2 or diseased LMT at initial CAG is an independent risk factor of in-hospital death in primary PCI-treated AMI patients requiring mechanical support devices.
[show abstract][hide abstract] ABSTRACT: An attenuated heart rate response to exercise, termed chronotropic incompetence (CI), has been reported to be an independent predictor of cardiovascular mortality. We examined the change in autonomic function during exercise testing and correlated the results with CI.
Exercise testing using a bicycle ergometer was performed in 172 patients who had no evidence of cardiac disease. Chronotropic incompetence was defined as the failure to achieve 85% of the age-predicted maximum heart rate, heart rate reserve <80%, or chronotropic response index <0.80. We analysed the relationship between CI and the change in two components of heart rate variability during exercise testing: high-frequency (HF) component (0.15-0.40 Hz) as an index of vagal modulation and the ratio of low-frequency (LF) component (0.04-0.15 Hz) to HF component as an index of sympathovagal balance. Heart rate variability indexes before exercise were similar in patients with and without CI. Percentage changes after exercise in the ratio of LF to HF component were higher in patients with CI than in those without CI (84 +/- 15 vs. 41 +/- 16%, P < 0.05), whereas percentage changes in an HF component were similar in the two groups.
Our data suggested that CI in patients without structural heart disease was mainly caused by a pathophysiological condition in which sympathetic activation was not well translated into heart rate increase. Further study is needed to determine the post-synaptic sensitivity of the beta-adrenergic receptor pathway in relation to CI.
[show abstract][hide abstract] ABSTRACT: Despite a great progress of modern reperfusion strategies in acute coronary syndrome (ACS), ischemic heart disease is still a leading course of mortality in the developed countries. Cell therapy is a promising option to treat ischemic heart disease refractory to conventional treatments. In particular, adult stem cells have been identified and used to clinical cases. Although the detail mechanisms to repair adult heart need further investigation, several clinical studies suggest its safety and feasibility. Current large-scale randomized study will reveal optimal strategy of cell therapy for the patients with ACS.
Nippon rinsho. Japanese journal of clinical medicine 04/2010; 68(4):726-30.
[show abstract][hide abstract] ABSTRACT: Predictors of suboptimal coronary flow in the infarct-related artery (IRA) after stent-based primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) have not been fully investigated.
Using the AMI-Kyoto Multi-Center Risk Study database, we retrospectively compared clinical manifestations and in-hospital prognosis between AMI patients undergoing stent-based primary PCI with final Thrombolysis In Myocardial Infarction (TIMI) grade < or = 2 in the IRA (nonoptimal group, n=69) and those with final TIMI grade 3 (optimal group, n=1200). The nonoptimal group had higher prevalence of Killip class > or = 3 at admission, higher frequency of mechanical support devices during procedures, larger value of maximal creatine phosphokinase, and a significantly higher in-hospital mortality rate (27.5% for nonoptimal vs. 9.0% for optimal, P<0.001), compared with the optimal group. On multivariate analysis, Killip class > or = 3 at admission was the independent predictor of the final nonoptimal flow (odds ratio 2.33, 95% confidence intervals 1.27-4.26 P=0.006), but TIMI 3 flow before primary PCI and elapsed time (symptom onset-to-admission time)<24h were not.
Killip class > or = 3 at admission is an independent predictor of the final nonoptimal flow in AMI patients undergoing primary PCI with stent implantation.
Journal of Cardiology 03/2010; 55(2):217-23. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: The plasma level of interleukin-6 (IL-6) has been reported to be associated with left ventricular (LV) remodelling after myocardial infarction (MI). The present study was designed to examine whether anti-IL-6 receptor antibody (MR16-1) prevents the development of LV remodelling after MI.
Balb/c male mice were subjected to MI by ligating the left anterior descending coronary artery. The mice were then treated with an intraperitoneal injection of MR16-1 (500 microg/body) or control IgG. MR16-1 decreased the myocardial myeloperoxidase activity and monocyte chemoattractant protein-1 concentration in the infarct region, concomitant with decreases in neutrophil and macrophage infiltration 3 days after ligation, while infarct size was comparable between the control IgG- and MR16-1-treated mice. At 7 days after ligation, MR16-1 significantly suppressed matrix metalloproteinase-2 activity in the infarct region. Furthermore, the MR16-1-treated mice demonstrated a reduction in LV dilatation and an improvement in LV contractile function compared with the control IgG-treated mice at 7 and 28 days after surgery, leading to an improvement in survival rate (80.6 vs. 59.5%, P < 0.05) at 28 days after surgery. The beneficial effects of MR16-1 were accompanied by histological suppression of cardiomyocyte hypertrophy and interstitial fibrosis in the non-infarct region.
Administration of MR16-1 after MI suppressed myocardial inflammation, resulting in the amelioration of LV remodelling. Neutralization of the IL-6 receptor is a potentially useful strategy for protecting hearts from LV remodelling after MI.
Cardiovascular research 03/2010; 87(3):424-30. · 5.80 Impact Factor