Bio

Honors & Awards


  • “Honors Scholarship”, Ministry of Education, Culture, Sports, Science and Technology of Japan (2004-2006)
  • Best paper award (Clinical/Preclinical/Translational research category), Society of Experimental biology and Medicine (2007)
  • Jay N. Cohn Young Investigator Award (Basic Science), Heart Failure Society of America (2008)
  • Early Career Author Award 2008, International Society of Heart Research/Journal of Molecular Cellular Cardiology. (2009)

Professional Education


  • Doctor of Philosophy, Niigata University (2006)
  • B Pharm, MGR Medical University, India, Pharmacy (1998)
  • M S, Punjabi University, India, Pharmacology (2002)
  • PhD, Niigata University of Pharmacy, Pharmaceutical Sciences (2006)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


Working on drug discovery research
I'm looking at pathophysiology of cardiovascular diseases and evluating potential agents for cardiac complications
PKC signaling in mast cells and in heart failure
ALDH in diabetic cardiomyopathy

Publications

Journal Articles


  • PKCßII inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses. Journal of cellular and molecular medicine Palaniyandi, S. S., Ferreira, J. C., Brum, P. C., Mochly-Rosen, D. 2011; 15 (8): 1769-1777

    Abstract

    Protein kinase C βII (PKCβII) levels increase in the myocardium of patients with end-stage heart failure (HF). Also targeted overexpression of PKCβII in the myocardium of mice leads to dilated cardiomyopathy associated with inflammation, fibrosis and myocardial dysfunction. These reports suggest a deleterious role of PKCβII in HF development. Using a post-myocardial infarction (MI) model of HF in rats, we determined the benefit of chronic inhibition of PKCβII on the progression of HF over a period of 6 weeks after the onset of symptoms and the cellular basis for these effects. Four weeks after MI, rats with HF signs that were treated for 6 weeks with the PKCβII selective inhibitor (βIIV5-3 conjugated to TAT(47-57) carrier peptide) (3 mg/kg/day) showed improved fractional shortening (from 21% to 35%) compared to control (TAT(47-57) carrier peptide alone). Formalin-fixed mid-ventricle tissue sections stained with picrosirius red, haematoxylin and eosin and toluidine blue dyes exhibited a 150% decrease in collagen deposition, a two-fold decrease in inflammation and a 30% reduction in mast cell degranulation, respectively, in rat hearts treated with the selective PKCβII inhibitor. Further, a 90% decrease in active TGFβ1 and a significant reduction in SMAD2/3 phosphorylation indicated that the selective inhibition of PKCβII attenuates cardiac remodelling mediated by the TGF-SMAD signalling pathway. Therefore, sustained selective inhibition of PKCβII in a post-MI HF rat model improves cardiac function and is associated with inhibition of pathological myocardial remodelling.

    View details for DOI 10.1111/j.1582-4934.2010.01174.x

    View details for PubMedID 20874717

  • Regulation of mitochondrial processes: a target for heart failure. Drug discovery today. Disease mechanisms Palaniyandi, S. S., Qi, X., Yogalingam, G., Ferreira, J. C., Mochly-Rosen, D. 2010; 7 (2): e95-e102

    Abstract

    Cardiac mitochondria, the main source of energy as well as free radicals, are vital organelles for normal functioning of the heart. Mitochondrial number, structure, turnover and function are regulated by processes such as mitochondrial protein quality control, mitochondrial fusion and fission and mitophagy. Recent studies suggest that abnormal changes in these mitochondrial regulatory processes may contribute to the pathology of heart failure (HF). Here we discuss these processes and their potential as therapeutic targets.

    View details for PubMedID 21278905

  • Protein kinase C in heart failure: a therapeutic target? CARDIOVASCULAR RESEARCH Palaniyandi, S. S., Sun, L., Batista Ferreira, J. C., Mochly-Rosen, D. 2009; 82 (2): 229-239

    Abstract

    Heart failure (HF) afflicts about 5 million people and causes 300,000 deaths a year in the United States alone. An integral part of the pathogenesis of HF is cardiac remodelling, and the signalling events that regulate it are a subject of intense research. Cardiac remodelling is the sum of responses of the heart to causes of HF, such as ischaemia, myocardial infarction, volume and pressure overload, infection, inflammation, and mechanical injury. These responses, including cardiomyocyte hypertrophy, myocardial fibrosis, and inflammation, involve numerous cellular and structural changes and ultimately result in a progressive decline in cardiac performance. Pharmacological and genetic manipulation of cultured heart cells and animal models of HF and the analysis of cardiac samples from patients with HF are all used to identify the molecular and cellular mechanisms leading to the disease. Protein kinase C (PKC) isozymes, a family of serine-threonine protein kinase enzymes, were found to regulate a number of cardiac responses, including those associated with HF. In this review, we describe the PKC isozymes that play critical roles in specific aspects of cardiac remodelling and dysfunction in HF.

    View details for DOI 10.1093/cvr/cvp001

    View details for Web of Science ID 000265095400008

    View details for PubMedID 19168855

  • Mast cells and epsilon PKC: A role in cardiac remodeling in hypertension-induced heart failure JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY Palaniyandi, S. S., Inagaki, K., Mochly-Rosen, D. 2008; 45 (6): 779-786

    Abstract

    Heart failure (HF) is a chronic syndrome in which pathological cardiac remodeling is an integral part of the disease and mast cell (MC) degranulation-derived mediators have been suggested to play a role in its progression. Protein kinase C (PKC) signaling is a key event in the signal transduction pathway of MC degranulation. We recently found that inhibition of epsilonPKC slows down the progression of hypertension-induced HF in salt-sensitive Dahl rats fed a high-salt diet. We therefore determined whether epsilonPKC inhibition affects MC degranulation in this model. Six week-old male Dahl rats were fed with a high-salt diet to induce systemic hypertension, which resulted in concentric left ventricular hypertrophy at the age of 11 weeks, followed by myocardial dilatation and HF at the age of 17 weeks. We administered epsilonV1-2, an epsilonPKC-selective inhibitor peptide (3 mg/kg/day), deltaV1-1, a deltaPKC-selective inhibitor peptide (3 mg/kg/day), TAT (negative control; at equimolar concentration; 1.6 mg/kg/day) or olmesartan (angiotensin receptor blocker [ARB] as a positive control; 3 mg/kg/day) between 11 weeks and 17 weeks. Treatment with epsilonV1-2 attenuated cardiac MC degranulation without affecting MC density, myocardial fibrosis, microvessel patency, vascular thickening and cardiac inflammation in comparison to TAT- or deltaV1-1-treatment. Treatment with ARB also attenuated MC degranulation and cardiac remodeling, but to a lesser extent when compared to epsilonV1-2. Finally, epsilonV1-2 treatment inhibited MC degranulation in isolated peritoneal MCs. Together, our data suggest that epsilonPKC inhibition attenuates pathological remodeling in hypertension-induced HF, at least in part, by preventing cardiac MC degranulation.

    View details for DOI 10.1016/j.yjmcc.2008.08.009

    View details for Web of Science ID 000261529000011

    View details for PubMedID 18804478

  • 14-3-3 protein regulates Ask1 signaling and protects against diabetic cardiomyopathy BIOCHEMICAL PHARMACOLOGY Thandavarayan, R. A., Watanabe, K., Ma, M., Veeyaveedu, P. T., Gurusamy, N., Palaniyandi, S. s., Zhang, S., Muslin, A. J., Kodama, M., Aizawa, Y. 2008; 75 (9): 1797-1806

    Abstract

    Mammalian 14-3-3 proteins are dimeric phosphoserine-binding proteins that participate in signal transduction and regulate several aspects of cellular biochemistry. Diabetic cardiomyopathy is associated with increased oxidative stress and inflammation. In order to study the pathogenic changes underlying diabetic cardiomyopathy, we examined the role of 14-3-3 protein and apoptosis signal-regulating kinase 1 (Ask1) signaling by using transgenic mice with cardiac-specific expression of a dominant-negative 14-3-3eta protein mutant (DN 14-3-3eta) after induction of experimental diabetes. The elevation in blood glucose was comparable between wild type (WT) and DN 14-3-3eta mice. However, a marked downregulation of thioredoxin reductase was apparent in DN 14-3-3eta mice compared to WT mice after induction of diabetes. Significant Ask1 activation in DN 14-3-3eta after diabetes induction was evidenced by pronounced de-phosphorylation at Ser-967 and intense immunofluorescence observed in left ventricular (LV) sections. Echocardiographic analysis revealed that cardiac functions were notably impaired in diabetic DN 14-3-3eta mice compared to diabetic WT mice. Marked increases in myocardial apoptosis, cardiac hypertrophy, and fibrosis were observed with a corresponding up-regulation of atrial natriuretic peptide and galectin-3, as well as a downregulation of sarcoendoplasmic reticulum Ca2+ ATPase2 expression. Furthermore, diabetic DN 14-3-3eta mice displayed significant reductions of platelet-endothelial cell adhesion molecule-1 staining as well as endothelial nitric acid synthase and vascular endothelial growth factor expression. In conclusion, our data suggests that enhancement of 14-3-3 protein could provide a novel therapeutic strategy against hyperglycemia-induced left ventricular dysfunction and can limit the progression of diabetic cardiomyopathy by regulating Ask1 signaling.

    View details for DOI 10.1016/j.bcp.2008.02.003

    View details for Web of Science ID 000255849400011

    View details for PubMedID 18342293

  • Effects of V-2-receptor antagonist tolvaptan and the loop diuretic furosemide in rats with heart failure BIOCHEMICAL PHARMACOLOGY Veeraveedu, P. t., Watanabe, K., Ma, M., Palaniyandi, S. s., Yamaguchi, K., Kodama, M., Aizawa, Y. 2008; 75 (6): 1322-1330

    Abstract

    Diuretics are frequently required to treat fluid retention in patients with chronic heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohormonal activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V(2) receptor (V(2)R) and its levels are increased in CHF. This study was conducted to characterize the diuretic effect of tolvaptan, a non-peptide AVP V(2)R antagonist, and furosemide, a loop diuretic in a rat model of CHF after experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan, and furosemide. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Tolvaptan produces a diuresis comparable to furosemide. Unlike tolvaptan, furosemide significantly increased urinary sodium and potassium excretion. Tolvaptan markedly elevated electrolyte-free water clearance (E-CH(2)O) or aquaresis to a positive value and increased urinary AVP excretion. In contrast to tolvaptan, furosemide elevated only electrolyte clearance (E-Cosm) but not E-CH(2)O. The differences in diuretic profile reflected the changes in plasma sodium and hormone levels. Tolvaptan dose dependently elevated plasma sodium concentration, but furosemide tended to decrease it. Furosemide significantly elevated plasma renin activity and aldosterone concentration. On the other hand, tolvaptan did not affect these parameters. Our results suggest that, tolvaptan have a potential medical benefit for the treatment of edematous conditions in CHF by removing excess water from the body without activating the RAAS or causing serum electrolyte imbalances.

    View details for DOI 10.1016/j.bcp.2007.11.011

    View details for Web of Science ID 000254687800008

    View details for PubMedID 18179782

  • Torasemide, a long-acting loop diuretic, reduces the progression of myocarditis to dilated cardiomyopathy EUROPEAN JOURNAL OF PHARMACOLOGY Veeraveedu, P. t., Watanabe, K., Ma, M., Palaniyandi, S. s., Yamaguchi, K., Suzuki, K., Kodama, M., Aizawa, Y. 2008; 581 (1-2): 121-131

    Abstract

    Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular dysfunction. However, nothing is known about the effect of torasemide on myocardial remodeling in a rat model in which myosin-induced experimental autoimmune myocarditis might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, we investigated the effects of torasemide on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in experimental autoimmune myocarditis rats. Diuresis was increased dose-dependently by torasemide; the urinary potassium and sodium excretion was significantly decreased and increased, respectively. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by torasemide treatment in a dose-dependent manner. The area of fibrosis, myocyte size and the myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase were significantly decreased, and the sarcoplasmic reticulum Ca2+ ATPase2 protein level was significantly increased by torasemide treatment. Moreover, the plasma levels of angiotensin II and aldosterone were increased and atrial natriuretic peptide was decreased in a dose-dependent manner. Our results indicate that torasemide treatment significantly improved left ventricular function and ameliorated the progression of cardiac remodeling beyond its renal effects in rats with chronic heart failure after experimental autoimmune myocarditis.

    View details for DOI 10.1016/j.ejphar.2007.11.034

    View details for Web of Science ID 000253575900015

    View details for PubMedID 18154949

  • Comparative effects of torasemide and furosemide in rats with heart failure BIOCHEMICAL PHARMACOLOGY Veeraveedu, P. t., Watanabe, K., Ma, M., Thandavarayan, R. A., Palaniyandi, S. s., Yamaguchi, K., Suzuki, K., Kodama, M., Aizawa, Y. 2008; 75 (3): 649-659

    Abstract

    It has been reported that torasemide but not furosemide, may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. We therefore compared the therapeutic effects of torasemide, a long-acting loop diuretic, and furosemide, a short-acting one, on the progression of LV remodeling in a rat model of chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM). CHF was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide, or vehicle. We investigated the effects on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in EAM rats. Diuresis was increased dose dependently by both torasemide and furosemide, showed an equipotent natriuretic effect. The urinary potassium excretion was significantly increased with furosemide in comparison to torasemide. Myocardial functional parameters were significantly improved by torasemide. Conversely, these parameters did not change in rats receiving furosemide. Torasemide suppressed LV fibrosis, myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase and improved survival rate to the control level, but furosemide did not. Moreover, both pharmacological interventions significantly elevated plasma angiotensin II and decreased atrial natriuretic peptide in a dose-dependent manner. Our results demonstrate that compared with furosemide, torasemide treatment significantly improved survival rate, LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

    View details for DOI 10.1016/j.bcp.2007.09.026

    View details for Web of Science ID 000253015200006

    View details for PubMedID 18001696

  • Effects of nonpeptide vasopressin V-2 antagonist tolvaptan in rats with heart failure BIOCHEMICAL PHARMACOLOGY Veeraveedu, P. t., Watanabe, K., Ma, M., Palaniyandi, S. s., Yamaguchi, K., Suzuki, K., Kodama, M., Aizawa, Y. 2007; 74 (10): 1466-1475

    Abstract

    Similar to other neurohormones that are activated in chronic heart failure (CHF), circulating arginine vasopressin (AVP) is elevated in patients with CHF. The precise role of AVP in the pathophysiology of cardiovascular disease is controversial. AVP is a peptide hormone that contributes to water retention and vasoconstriction in CHF through effects on V(2) and V(1a) receptors, respectively. In the present study, the effect of V(2) receptor (V(2)R) blockade using tolvaptan was assessed in a rat model of myosin-induced experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan (3 or 10mg/(kg day)) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Chronic V(2)R blockade increased urine volume and urinary AVP excretion and decreased urine osmolality but had no natriuretic effect, and as a result caused increases in plasma osmolality and sodium. High doses of tolvaptan markedly elevated electrolyte-free water clearance. V(2)R blockade did not activate the renin-angiotensin system, not influence cardiac remodeling, cardiac function, or survival. The upregulation of aquaporin 2 protein in the kidney of CHF rats was inhibited by the administration of V(2)R antagonist. These results suggest that in a rat model of CHF, AVP plays a major role in water retention through the renal V(2)R.

    View details for DOI 10.1016/j.bcp.2007.07.027

    View details for Web of Science ID 000251118400004

    View details for PubMedID 17720144

  • Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats EXPERIMENTAL BIOLOGY AND MEDICINE Palaniyandi, S. s., Nagai, Y., Watanabe, K., Ma, M., Veeraveedu, P. t., Prakash, P., Kamal, F. A., Abe, Y., Yamaguchi, K., Tachikawa, H., Kodama, M., Aizawa, Y. 2007; 232 (9): 1213-1221

    Abstract

    Chymase has been known as a local angiotensin II-generating enzyme in the cardiovascular system in dogs, monkeys, hamsters, and humans; however, recently it was reported that chymase also has various other functions. Therefore, we decided to examine whether the inhibition of chymase improves disease conditions associated with the pathophysiology of dilated cardiomyopathy in rats and its possible mechanism of action as rat chymase is unable to produce angiotensin II. We examined the effect of TY-51469, a novel chymase inhibitor (0.1 mg/kg/day [group CYI-0.1, n = 15] and 1 mg/kg/day [group CYI-1, n = 15]), in myosin-immunized postmyocarditis rats. Another group of myosin-immunized rats was treated with vehicle (group V, n = 15). Age-matched normal rats without immunization (group N, n = 10) were also included in the study. After 4 weeks of treatment, we evaluated cardiac function; area of fibrosis; fibrogenesis; levels of transforming growth factor (TGF)-beta1 and collagen III; hypertrophy and its marker, atrial natriuretic peptide (ANP); and mast cell activity. Survival rate and myocardial functions improved dose-dependently with chymase inhibitor treatment after myosin immunization. A reduction in the percent area of myocardial fibrosis, fibrogenesis, myocardial hypertrophy, and mast cell activity along with a reduction in TGF-beta1, collagen III, and ANP levels in the myocardium were noted in postmyocarditis rats that received chymase inhibitor treatment. The treatment also decreased myocardial aldosterone synthase levels in those animals. Inhibition of chymase reduces the pathogenesis of postmyocarditis dilated cardiomyopathy and progression to heart failure by preventing the pathological remodeling and residual inflammation in rats.

    View details for DOI 10.3181/0703-RM-85

    View details for Web of Science ID 000249887500010

    View details for PubMedID 17895529

  • Blockade of interferon-gamma-inducible protein-10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells PATHOLOGY INTERNATIONAL Suzuki, K., Kawauchi, Y., Palaniyandi, S. s., Veeraveedu, P. t., Fujii, M., Yamagiwa, S., Yoneyama, H., Han, G. D., Kawachi, H., Okada, Y., Ajioka, Y., Watanabe, K., Hosono, M., Asakura, H., Aoyagi, Y., Narumi, S. 2007; 57 (7): 413-420

    Abstract

    The role of chemokines, especially CXCL10/interferon-gamma-inducible protein 10 kDa (IP-10), a chemokine to attract CXCR3(+) T-helper 1-type CD4(+) T cells, is largely unknown in the pathophysiology of inflammatory bowel disease; ulcerative colitis and Crohn's disease. The authors have earlier shown that IP-10 neutralization protected mice from acute colitis by protecting crypt epithelial cells of the colon. To investigate the therapeutic effect of neutralization of IP-10 on chronic colitis, an anti-IP-10 antibody was injected into mice with newly established murine AIDS (MAIDS) colitis. Anti-IP-10 antibody treatment reduced the number of colon infiltrating cells when compared to those mice given a control antibody. The treatment made the length of the crypt of the colon greater than control antibody. The number of Ki67(+) proliferating epithelial cells was increased by the anti-IP-10 antibody treatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)(+) apoptotic cells were observed in the epithelial cells of the luminal tops of crypts in control MAIDS colitis, whereas TUNEL(+) apoptotic epithelial cells were rarely observed with anti-IP-10 antibody treatment. In conclusion, blockade of IP-10 attenuated MAIDS colitis through blocking cellular trafficking and protecting intestinal epithelial cells, suggesting that IP-10 plays a key role in the development of inflammatory bowel disease as well as in chronic experimental colitis.

    View details for DOI 10.1111/j.1440-1827.2007.02117.x

    View details for Web of Science ID 000247477800003

    View details for PubMedID 17587240

  • Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Kawauchi, Y., Suzuki, K., Watanabe, S., Yamagiwa, S., Yoneyama, H., Han, G. D., Palaniyandi, S. s., Veeraveedu, P. t., Watanabe, K., Kawachi, H., Okada, Y., Shimizu, F., Asakura, H., Aoyagi, Y., Narumi, S. 2006; 291 (2): G345-G354

    Abstract

    Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-gamma-inducible protein 10 (IP-10), a chemokine to attract CXCR3+ T helper 1-type CD4+ T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-gamma+ and IL10+ cells in the mLN but significantly reduced their numbers, especially IFN-gamma+ and IL-10+ CD4+ T cells and IFN-gamma+ Mac-1+ cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+ T cells and IFN-gamma+ Mac-1+ cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.

    View details for DOI 10.1152/ajpgi.00002.2006

    View details for Web of Science ID 000238841300020

    View details for PubMedID 16825661

  • Comparative effects of pranidipine with amlodipine in rats with heart failure PHARMACOLOGY Veeraveedu, P. t., Watanabe, K., Ma, M., Gurusamy, N., Palaniyandi, S. s., Wen, J., Prakash, P., Wahed, M. I., Kamal, F. A., Mito, S., Kunisaki, M., Kodama, M., Aizawa, Y. 2006; 77 (1): 1-10

    Abstract

    The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and +/-dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-alpha, and improved sarcoplasmic reticulum Ca2+ ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.

    View details for DOI 10.1159/000091746

    View details for Web of Science ID 000237536700001

    View details for PubMedID 16508340

  • Inhibition of mast cells by interleukin-10 gene transfer contributes to protection against acute myocarditis in rats EUROPEAN JOURNAL OF IMMUNOLOGY Palaniyandi, S. S., Watanabe, K., Ma, M. L., Tachikawa, H., Kodama, M., Aizawa, Y. 2004; 34 (12): 3508-3515

    Abstract

    Progression of acute myocarditis involves a variety of inflammatory events. Mast cells have been implicated as the source of various cytokines, chemokines and histamine in acute inflammation and fibrosis. Interleukin (IL)-10 has well-known immunomodulatory actions that are exerted during the recovery phase of myocarditis. In this study, 9-week-old male Lewis rats were immunized with cardiac myosin. A plasmid vector expressing mouse IL-10 cDNA (800 mug per rat) was then transferred three times (7, 12 and 17 days after immunization) into the tibialis anterior muscles of the rats by electroporation. Microscopic examination of mast cells was carried out on toluidine blue-stained transverse sections of the mid ventricles. Mouse IL-10 gene transfer significantly reduced mast cell density, cardiac histamine concentration and mast cell growth, and prevented mast cell degranulation. Furthermore, improvement in both myocardial function and the overall condition of the rats was evident from the reduction in the heart weight-to-body weight ratio and inflammatory infiltration as well as improvement in hemodynamic and echocardiographic parameters. These findings suggest that IL-10 gene transfer by electroporation protected against myocarditis via mast cell inhibition.

    View details for Web of Science ID 000225677200022

    View details for PubMedID 15549732

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