Characterization of Cardiac Size and Function in SHRSP.Z-Leprfa/IzmDmcr Rats, a New Animal Model of Metabolic Syndrome

Abstract

Lifestyle-related diseases-visceral obesity, hypertension, dyslipidemia and glucose intolerance-are known to appear in a cluster referred to as metabolic syndrome. As the number of disease components in metabolic syndrome increases in a patient, the structure and function of the heart becomes more compromised. 1) For example, metabolic syndrome increases the risk of atrial enlargement and fibrillation 2,3) and left ventricular hypertrophy and diastolic dysfunction. 1,4) These structural and functional abnormalities are considered to contribute to the increased cardiovascular morbidity and mortality associated with metabolic syndrome. However, the mechanisms underlying these abnormalities are not well understood.SHRSP.Z-Lepr fa /IzmDmcr rats (SHRSP-fatty) were established by crossing stroke-prone SHR (SHRSP/Izm) with Zucker obese rats to create a new animal model of metabolic syndrome.5) These rats develop spontaneous severe hypertension and obesity, and exhibit metabolic abnormalities (dyslipidemia, hyperinsulinemia and hyperglycemia), which are similar to those found in human metabolic syndrome. To date SHRSP-fatty have been used in studies that evaluated dysfunction of vasodilation mechanisms, cardiovascular remodeling, and atherogenic dyslipidemia in metabolic syndrome. [6][7][8] The aim of the present study was to characterize the cardiac structure and function in SHRSP-fatty. Increased cardiac stiffness induced by disturbed myocardial collagen turnover is suggested as one of the mechanisms of cardiac abnormalities in hypertension and diabetes.9,10) Therefore, as structural parameters, heart weight and a major myocardial collagen, collagen type I, as an index of fibrosis, were measured. Additionally, collagen type III, which contributes to tissue elasticity, was measured and the ratio of type I to type III was calculated as an index of myocardial stiffness. To assess cardiac function in SHRSP-fatty, heart rate, systolic blood pressure, cardiac output, blood flow and stroke volume were measured by tail-cuff and plethysmography, and compared to those in hypertensive lean SHRSP and normotensive lean WistarKyoto rats (WKY). Systolic and diastolic cardiac functions were also determined by echocardiography. The results may inform us whether this model would be a useful animal model to evaluate cardiac complications of metabolic syndrome. MATERIALS AND METHODS Experimental AnimalsMale SHRSP-fatty (nϭ18), SHRSP (nϭ18) and normotensive control WKY (nϭ18) were purchased at 16 weeks of age from Japan SLC, Inc. (Hamamatsu, Japan). The rats were established by the Disease Model Cooperative Research Association (Hamamatsu, Japan). Standard chow (CE-2; Clea Japan Inc., Tokyo, Japan) and water were available ad libitum during the experimental period. The study protocols were performed according to the Guideline for the Care and Use of Laboratory Animals approved by Mukogawa Women's University.Tail-Cuff Method and Plethysmography Systolic blood pressure and heart rate of conscious rats were meas- Cardiac structural and funct...

Abnormal amounts of intracellular calcium regulatory proteins in SHRSP.Z-Leprfa/IzmDmcr rats with metabolic syndrome and cardiac dysfunction

“…SHRSP fatty rats exhibit major biochemical features of metabolic syndrome, in that they spontaneously develop obesity and severe hypertension, and exhibit hyperlipidemia and abnormal glucose tolerance at an early age (Hiraoka-Yamamoto et al 2004;Ueno et al 2008). We have demonstrated that impaired coronary vasodilation, ventricular hypertrophy, and diastolic dysfunction occur in SHRSP fatty rats Tada et al 2010), as shown in metabolic syndrome in humans (Guize et al 2008). SHRSP fatty rats may therefore be a useful model for evaluating the pathogenesis of cardiac dysfunction in metabolic syndrome.…”

APOE*3Leiden.CETP transgenic mice as model for pharmaceutical treatment of the metabolic syndrome

“…Conversely, consumption of fructose enhances plasma triglycerides by stimulation of de novo lipogenesis in rodents and man [30] and simultaneously lowers HDL in CETP carrying species. the SHRSP fatty rats, Nile grass rats and Israeli sand rats [31][32][33]. Other animal models have been described that also possess this combination of features, e.g.…”

A maternal high salt diet disturbs cardiac and vascular function of offspring

“…Ventricular tissue samples were removed, homogenized in lysis buffer with dithiothreitol (DTT), and centrifuged (10,000 g) for 15 min at 4°C [43]. Western blots were performed on supernatants with antibodies to phospholamban (PLB) monomers (1:5000 dilution, Abcam PLC, Cambridge, UK), phosphorylated-PLB (Ser16) (1:1000 dilution, Santa Cruz Biotechnology Inc., CA, USA), sarco/endoplasmic reticulum Ca 2 + -ATPase (SERCA) 2 (1:1000 dilution, Thermo Fisher Scientific Inc., MA, USA) and α-sarcomeric actin (Sigma-Aldrich Co., Missouri, USA, 1:20,000).…”