A pinboard by
Faheem Sultan

PhD Scholar, Guru Angad Dev Veterinary and Animal Sciences University


Cardiovascular diseases still remain the leading cause of death globally. Out of the various cardiovascular problems, ischemic heart disease (IHD) contributes to the maximum number of deaths. Apart from humans, cardiovascular disorders in canines are of major importance in terms of animal health and welfare. . Myocardial necrosis due to myocardial ischemia, known as myocardial infarction, is a serious manifestation of IHD. Use of animal models for ischemic heart disease has considerably contributed to the understanding of patho-physiological mechanisms of heart ailments and the development of new therapeutic strategies to treat and prevent ischemic heart disease. I am trying to study the pleiotropic effects of various drugs that could potentially serve as alternative agents in the prevention and treatment of pathological hypertrophy and heart failure. Thus, gaining an expanded understanding of the signaling pathways mediated by those drugs may lead to the development of novel agents for the prevention and treatment of cardiovascular diseases


Critical role of TNF inhibition in combination therapy for elderly mice with atherosclerosis.

Abstract: We have previously shown that the combination of pravastatin and sarpogrelate is synergistically beneficial for atherosclerosis. In this study, we investigated whether the pravastatin-sarpogrelate combination was sufficient for treatment in an old mouse model of atherosclerosis or if additional intervention would be needed to address the newly included aging factor and its complex pathophysiological impact on the atherosclerogenic state. We added an anti-TNF biologic to the combination treatment cocktail because of the known pathologic roles of TNF in the aging process. Sixty-week-old low-density lipoprotein receptor knockout mice were fed a high-fat, high-cholesterol diet and treated with the sarpogrelate and pravastatin combination, etanercept alone, or the triple combination. Although, etanercept alone did not significantly reduce aortic root and atherosclerotic plaque areas, the pravastatin-sarpogrelate combination and pravastatin-sarpogrelate-etanercept triple therapy significantly reduced the plaque areas. Surprisingly, TNF-inhibition was critically required to reduce the plaque areas of aortic roots and the expression of ICAM-1, MOMA-2, and TNF. More importantly, a lipid-lowering effect by pravastatin was observed only in the triple therapy group and not in the pravastatin and sarpogrelate combination group. These results suggest that TNF-inhibitory intervention should be added to the conventional therapy as a novel strategy for treating the elderly patients with atherosclerosis. This article is protected by copyright. All rights reserved.

Pub.: 24 Jun '17, Pinned: 13 Aug '17

Inhibition of mevalonate pathway prevents ischemia-induced cardiac dysfunction in rats via RhoA-independent signaling pathway.

Abstract: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction.We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI). After MI, adult male Sprague-Dawley rats were treated with drugs that antagonize key components in mevalonate pathway, including 3-hydroxy-3-methylglutaryl-CoA reductase, farnesyl pyrophosphate synthase and Rho-kinase for 10 weeks. The protein expression of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca(2+) ATPase (SERCA) 2a, phospholamban (PLB), phospho-PLB at serine-16 (PSer16-PLB), FKBP12.6 and RhoA as well as RyR2 and FKBP12.6 mRNA levels were evaluated.Rosuvastatin and alendronate treatment prevented myocardial remodeling, improved cardiac function and reduced infarct size. Furthermore, rosuvastatin and alendronate promoted an increase in the protein expression of SERCA2a and PSer16-PLB/PLB ratio as well as partially restored the RyR2 and FKBP12.6 gene and protein expression. Fasudil failed to exert these beneficial effects.The present findings indicate that mevalonate pathway inhibition by rosuvastatin and alendronate prevent cardiac remodeling and dysfunction possibly through RhoA-independent mechanisms. This article is protected by copyright. All rights reserved.

Pub.: 01 Jul '17, Pinned: 13 Aug '17

High Dose Humanin Analogue Applied During Ischemia Exerts Cardioprotection Against Ischemia/Reperfusion Injury by Reducing Mitochondrial Dysfunction.

Abstract: Although the gold standard treatment for acute myocardial infarction is reperfusion therapy, reperfusion itself can cause myocardial damage via induction of cardiac mitochondrial dysfunction. This can lead to increased myocardial infarct size, arrhythmias and left ventricular (LV) dysfunction. Recently, a newly discovered peptide, Humanin, has been shown to exert several beneficial effects including anti-oxidative and anti-apoptosis effects. We recently reported that a Humanin analogue (HNG, 84 μg/kg) given prior to cardiac ischemia exerted cardioprotection against I/R injury, but failed to do so when it was given after ischemia was induced. However, in a clinical setting, patients can only be treated after the onset of ischemia. In this study, we investigated the potential benefit of various doses of HNG therapy (84, 168, 252 μg/kg) against myocardial I/R injury when applied during ischemia on cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial function and LV function METHODS: Myocardial I/R injury was induced in rats by 30-minute left anterior descending coronary artery occlusion, followed by 120-minute of reperfusion. HNG at the different doses were given intravenously at 15 min after ischemic onset and also at the onset of reperfusion RESULTS: HNG (252 μg/kg) applied during the ischemic period not only increased HN levels in the damaged myocardium, but also significantly decreased cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial dysfunction and left ventricular dysfunction. These benefits were mediated through the attenuation of cardiac mitochondrial dysfunction CONCLUSIONS: High-dose HN applied during ischemia in rats could exert cardioprotection against I/R injury-induced mitochondrial dysfunction. This article is protected by copyright. All rights reserved.

Pub.: 21 Jul '17, Pinned: 13 Aug '17