Sumanth D Prabhu

Sumanth D Prabhu
University of Alabama at Birmingham | UAB · Division of Cardiovascular Disease

MD

About

253
Publications
13,514
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
10,073
Citations
Citations since 2016
62 Research Items
5922 Citations
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
Additional affiliations
September 2011 - present
University of Alabama at Birmingham
Position
  • Managing Director

Publications

Publications (253)
Article
Background: Coronary vasomotion abnormalities have been described in small studies but not studied systematically. We aimed to review the present literature and analyze it to improve our understanding of chronic kidney disease (CKD) related-coronary microvascular dysfunction. Objective: Coronary flow reserve (CFR) is a well-known measure of coro...
Article
Ischemic heart failure (HF) is associated with elevated inflammatory responses including pro-inflammatory cytokines, such as Tumor necrosis factor (TNF) α [and its cognate receptors, TNF receptor (TNFR) 1 and TNFR2] and pathological switching of CD4 ⁺ T-cells. TNF-TNFR2 signaling is known to promote CD4 ⁺ T-cell activation and proliferation. Howeve...
Article
Background: The tyrosine kinase inhibitor (TKI) ponatinib is the oral drug for the treatment of chronic myelogenous leukemia (CML) patients with T315I (gatekeeper) mutation. Pharmacovigilance analysis of FDA and WHO datasets have revealed that ponatinib is the most cardiotoxic agent among all FDA-approved TKIs in a real-world scenario. However, the...
Article
Full-text available
Reperfusion injury after extended ischemia accounts for approximately 50% of myocardial infarct size, and there is no standard therapy. HDAC inhibition reduces infarct size and enhances cardiomyocyte autophagy and PGC1α-mediated mitochondrial biogenesis when administered at the time of reperfusion. Furthermore, a specific autophagy-inducing peptide...
Article
Full-text available
CD4⁺ T cells turn pathological during heart failure (HF). We show that the expression of tumor necrosis factor α (TNF-α) and tumor necrosis factor receptor (TNFR1) increases in HF-activated CD4⁺ T cells. However, the role of the TNF-α/TNFR1 axis in T-cell activation/proliferation is unknown. We show that TNFR1 neutralization during T-cell activatio...
Article
Full-text available
Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation...
Article
Full-text available
Circadian clocks regulate numerous biological processes, at whole body, organ, and cellular levels. This includes both hormone secretion and target tissue sensitivity. Although growth hormone (GH) secretion is time-of-day-dependent (increased pulse amplitude during the sleep period), little is known regarding whether circadian clocks modulate GH se...
Article
Full-text available
Introduction : The interplay between sleep duration and inflammation on the baseline and incident cardiovascular (CV) risk is unknown. We sought to evaluate the association between sleep duration, C-reactive protein (CRP), baseline CV risk, and incident CV mortality. Methods : We used data from the National Health and Nutrition Examination Survey...
Article
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who die...
Article
Full-text available
Essentially all biological processes fluctuate over the course of the day, manifesting as time-of-day-dependent variations with regards to the way in which organ systems respond to normal behaviors. For example, basic, translational, and epidemiologic studies indicate that temporal partitioning of metabolic processes governs the fate of dietary nut...
Article
Objective To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease. Methods We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte co...
Article
Introduction: Inflammation is associated with worse cardiovascular (CV) prognosis. We evaluated the impact of adding elevated monocyte lymphocyte ratio (MLR) to 10-year atherosclerotic CV disease (ASCVD) risk score. Hypothesis: Adding elevated MLR improves risk classification by 10-year ASCVD risk score. Methods: We used data from 6 cycles of NHANE...
Article
Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Infiltrating Ly6C hi blood monocytes are a key component of this healing response; however, the importance of other monocyte/macrophage populations is unclear. Here, we demonstrate in mice an essential role fo...
Article
Background and Hypothesis: Reperfusion injury accounts for ~50% of myocardial infarct size, and clinically efficacious therapies are lacking. Histone deacetylase (HDAC) inhibition enhances cardiomyocyte autophagic activity, mitochondria biogenesis, and blunts ischemia/reperfusion (I/R) injury when given at the time of reperfusion. However, as HDAC...
Article
Introduction: Sleep disturbance is associated with higher inflammation and cardiovascular mortality. The interplay between sleep duration and inflammation as an effect modifier for cardiovascular risk is unknown. Hypothesis: We sought to evaluate the association between sleep duration, C-reactive protein (CRP), and cardiovascular mortality. Methods...
Article
Chronic inflammation contributes significantly to disease progression in heart failure (HF), and is characterized by expansion of activated macrophages, dendritic cells, and T cells in the failing heart. Neutrophils play a well-known role as the initial drivers of inflammatory response to myocardial infarction (MI), thereby providing the platform f...
Conference Paper
Background: Literature suggests that low hemoglobin (Hb) concentration in heart failure with a preserved ejection fraction (HFpEF) increases the risk of mortality and hospitalization. However, it is not clear what drives this increased risk of mortality. We evaluated the association of Hb with cause-specific mortality in HFpEF. Hypothesis: Low Hb...
Article
Introduction: Human genetic studies have shown a greater risk of cardiometabolic disease with genetically lower natriuretic peptide (NP) levels. We have previously shown that blacks have lower NP levels than whites albeit in older individuals, which is partly explained by genetic factors. A high-carbohydrate challenge in young healthy whites was as...
Article
Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 anti...
Article
12/15 lipoxygenase (LOX) directs inflammation and lipid remodeling. However, the role of 12/15LOX in post-myocardial infarction (MI) left ventricular remodeling is unclear. To determine the role of 12/15LOX, 8-12 week-old C57BL/6 J wild-type (WT; n = 93) and 12/15LOX-/-(n = 97) mice were subjected to permanent coronary artery ligation and monitored...
Article
Full-text available
Highlights • Hypothesis: CCR2⁺ monocyte-derived cardiac macrophages are required for adverse LV remodeling, cardiac T-cell expansion, and the transition to HF following pressure overload. • The imposition of pressure overload via TAC resulted in the early up-regulation of CCL2, CCL7, and CCL12 chemokines in the LV, increased Ly6ChiCCR2⁺ monocytes i...
Article
Full-text available
Following myocardial infarction (MI), overactive inflammation remodels the left ventricle (LV) leading to heart failure coinciding with reduced levels of 15-epi-Lipoxin A4 (15-epi LXA4). However, the role of 15-epi LXA4 in post-MI acute inflammatory response and resolving phase is unclear. We hypothesize that liposomal fusion of 15-epi-LXA4 (Lipo-1...
Article
Importance Recent studies have suggested that the natriuretic peptide system may be endogenously suppressed in black individuals who are free of prevalent cardiovascular disease. Whether natriuretic peptide levels contribute to racial disparities in clinical outcomes is unknown. Objective To examine racial differences in N-terminal pro–B-type natr...
Article
Background: The stress kinase c-jun N-terminal kinase (JNK) is critical in the pathogenesis of cardiac diseases associated with an increased incidence of atrial fibrillation (AF), the most common arrhythmia in the elderly. We recently discovered that JNK activation is linked to the loss of gap junction connexin43 (Cx43) and enhanced atrial arrhyth...
Article
Full-text available
Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functio...
Article
Whether and how fat intake contributes to persistent inflammation in obesity is unclear. Here, we report the differential metabolic transformation of fatty acids in heart failure (HF) pathology in the setting of obesity. We used permanent coronary ligation to induce myocardial infarction (MI) leading to acute (d1), healing phase (d5) and subsequent...
Article
Full-text available
Background In patients with non‐ST‐segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet agg...
Article
Because the fundamental defect in both acute myocardial infarction (MI) and ischemic cardiomyopathy is myocyte loss, stem cell therapy to regenerate lost myocardium is conceptually appealing. Multiple clinical trials have been performed in patients with acute MI and chronic ischemic heart failure using a variety of cell types, including bone marrow...
Article
Full-text available
The metabolic transformation of fatty acids to form oxylipids using 12/15lipoxygenase (LOX) can promote either resolving or non-resolving inflammation. However, the mechanism of how 12/15LOX interacts with PUFA (polyunsaturated fatty acids) in post-myocardial infarction (MI) healing is unclear. Here, we reported the role of 12/15LOX in post-MI card...
Article
Full-text available
The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not...
Article
Background: Inappropriately sustained inflammation is a hallmark of chronic ischemic heart failure (HF); however, the pathophysiological role of T lymphocytes is unclear. Methods and results: Permanent coronary ligation was performed in adult C57BL/6 mice. When compared with sham-operated mice, mice with HF (8 weeks after ligation) exhibited the...
Article
Full-text available
In the failing heart, iNOS is expressed by both macrophages and cardiomyocytes. We hypothesized that inflammatory cell-localized iNOS exacerbates left ventricular (LV) remodeling. Wild-type (WT) C57BL/6 mice underwent total body irradiation and reconstitution with bone marrow from iNOS−/− mice (iNOS−/−c) or WT mice (WTc). Chimeric mice underwent co...
Article
Continuous-flow left ventricular assist devices (CF LVADs) are rotary blood pumps that improve mean blood flow, but with potential limitations of non-physiological ventricular volume unloading and diminished vascular pulsatility. In this study, we tested the hypothesis that left ventricular unloading with increasing CF LVAD flow increases myocardia...
Article
Full-text available
Background Although cardiac and splenic mononuclear phagocytes (MPs), i.e., monocytes, macrophages and dendritic cells (DCs), are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling i...
Data
Effects of splenectomy on cardiac remodeling in pressure-overload heart failure (HF). A, Schematic of experimental protocol. B, Kaplan-Meier survival curves for sham-operated and TAC mice with and without splenectomy (n = 5–6 per group). C-D, Quantitative group data for LV ejection fraction (EF), LV end-diastolic volume (EDV), end-systolic volume (...
Data
Splenic monocyte populations during cardiac pressure-overload. A. Representative flow cytometry gating strategy for splenic Ly6C+ monocytes B. Quantitative group data for overall monocytes (Lin−CD11b+), pro-inflammatory monocytes (Lin−CD11b+Ly6Chi), and patrolling monocytes (Lin−CD11b+Ly6Clow) in the spleen during the indicated time points after TA...
Data
Circulating and splenic dendritic cell (DC) populations during cardiac pressure overload. A, Representative flow cytometry gating strategy for circulating and splenic DCs. B, Quantitative group data for DC subsets: Lin−CD11c+ total DCs, Lin−CD11clowB220+ plasmacytoid DCs and Lin−CD11c+B220− classical DCs during the indicated time points after TAC o...
Article
Full-text available
Cardiomyopathies are a leading cause of heart failure and are often caused by mutations in sarcomeric genes, resulting in contractile dysfunction and cellular damage. This may stimulate the production of a robust proinflammatory response. To determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (...
Article
Full-text available
Background: Therapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF). Methods: We examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medi...
Article
Full-text available
Post-myocardial infarction (MI), overactive inflammation is the hallmark of aging, however, the mechanism is unclear. We hypothesized that excess influx of omega 6 fatty acids may impair resolution, thus impacting the cardiosplenic and cardiorenal network post-MI. Young and aging mice were fed on standard lab chow (LC) and excess fatty acid (safflo...
Article
The incidence of cognitive impairment in cardiovascular disease (CVD) patients has increased, adversely impacting quality of life and imposing a significant economic burden. Brain imaging of CVD patients has detected changes in the hippocampus, a brain region critical for normal learning and memory. However, it is not clear whether adverse cardiac...
Article
Despite expansion of resident cardiac stem cells (CSCs; c-kit ⁺ Lin ⁻ ) after myocardial infarction, endogenous repair processes are insufficient to prevent adverse cardiac remodeling and heart failure (HF). This suggests that the microenvironment in post-ischemic and failing hearts compromises CSC regenerative potential. Inflammatory cytokines, su...
Article
In adult mammals, massive sudden loss of cardiomyocytes after infarction overwhelms the limited regenerative capacity of the myocardium, resulting in the formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimulation of toll-like receptor sign...
Article
Background: Heart failure is the leading cause for 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act. There is a growing interest in understanding the impact of evidence-based heart failure therapy on 30-day all-cause readmission. In the current study, we examined the impact of angiotensin-converting enzyme...
Article
Full-text available
Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricula...
Article
The cardioprotective inducible enzyme heme oxygenase-1 (HO-1) degrades prooxidant heme into equimolar quantities of carbon monoxide, biliverdin, and iron. We hypothesized that HO-1 mediates cardiac protection, at least in part, by regulating mitochondrial quality control. We treated WT and HO-1 transgenic mice with the known mitochondrial toxin, do...
Article
Background The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress. Objectives This...
Article
A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby a...
Article
Full-text available
In both preclinical and clinical studies, cell transplantation of several cell types is used to promote repair of damaged organs and tissues. Nevertheless, despite the widespread use of such strategies, there remains little understanding of how the efficacy of cell therapy is regulated. We showed previously that augmentation of a unique, metabolica...
Article
Background: We presented data that demonstrating that acute kidney injury (AKI) as defined by a rise in admission serum creatinine by ≥0.3mg/dL is associated with a 16% significant increase in 30-day all-cause readmission in hospitalized heart failure (HF) patients (Circulation. 2014; 130: A19999). We have previously published data suggesting that...