OBJECTIVES: We examined the effects of early treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on the progression of glucose intolerance and cardiovascular remodeling in a model of spontaneously developing type II diabetes mellitus (DM), the Otsuka Long-Evans Tokushima Fatty (OLETF) rats. BACKGROUND: Clinical trials showed that pravastatin prevented new-onset DM in hypercholesterolemic patients, and that it was effective in prevention of cardiovascular events in diabetics. METHODS: The OLETF rats were treated with pravastatin (100 mg/kg/day) from 5 weeks of age and compared with age-matched untreated OLETF rats and normal Long-Evans Tokushima Otsuka (LETO) rats on serial oral glucose tolerance tests (OGTT) and Doppler echocardiography and on histopathological/biochemical analyses of the heart at 30 weeks. RESULTS: The OGTT revealed that 40% and 89% of untreated OLETF rats were diabetic at 20 and 30 weeks, respectively, but 0% and only 30%, respectively, were diabetic in the treated OLETF. Left ventricular diastolic function was found impaired from 20 weeks in untreated OLETF but remained normal in the treated-OLETF. The wall-to-lumen ratio and perivascular fibrosis of coronary arteries were increased in untreated-OLETF but were limited in the treated-OLETF at 30 weeks. Moreover, cardiac expressions of a fibrogenic growth factor, transforming growth factor-beta1 (TGF-beta1), and a proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), were increased in untreated-OLETF. However, in the treated-OLETF, overexpressions of TGF-beta1 and MCP-1 were attenuated, which was associated with overexpression of endothelial nitric oxide synthase (eNOS) (2.5-fold of control LETO). CONCLUSIONS: Early pravastatin treatment prevented cardiovascular remodeling in the spontaneous DM model by retarding the progression of glucose intolerance, overexpressing cardiac eNOS, and inhibiting overexpressions of fibrogenic/proinflammatory cytokines.
OBJECTIVES: We examined the effects of early treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on the progression of glucose intolerance and cardiovascular remodeling in a model of spontaneously developing type II diabetes mellitus (DM), the Otsuka Long-Evans Tokushima Fatty (OLETF) rats. BACKGROUND: Clinical trials showed that pravastatin prevented new-onset DM in hypercholesterolemicpatients, and that it was effective in prevention of cardiovascular events in diabetics. METHODS: The OLETFrats were treated with pravastatin (100 mg/kg/day) from 5 weeks of age and compared with age-matched untreated OLETFrats and normal Long-Evans Tokushima Otsuka (LETO) rats on serial oral glucose tolerance tests (OGTT) and Doppler echocardiography and on histopathological/biochemical analyses of the heart at 30 weeks. RESULTS: The OGTT revealed that 40% and 89% of untreated OLETFrats were diabetic at 20 and 30 weeks, respectively, but 0% and only 30%, respectively, were diabetic in the treated OLETF. Left ventricular diastolic function was found impaired from 20 weeks in untreated OLETF but remained normal in the treated-OLETF. The wall-to-lumen ratio and perivascular fibrosis of coronary arteries were increased in untreated-OLETF but were limited in the treated-OLETF at 30 weeks. Moreover, cardiac expressions of a fibrogenic growth factor, transforming growth factor-beta1 (TGF-beta1), and a proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), were increased in untreated-OLETF. However, in the treated-OLETF, overexpressions of TGF-beta1 and MCP-1 were attenuated, which was associated with overexpression of endothelial nitric oxide synthase (eNOS) (2.5-fold of control LETO). CONCLUSIONS: Early pravastatin treatment prevented cardiovascular remodeling in the spontaneous DM model by retarding the progression of glucose intolerance, overexpressing cardiac eNOS, and inhibiting overexpressions of fibrogenic/proinflammatory cytokines.
Authors: Syed Usman Bin Mahmood; Camilo A Velasquez; Mohammad A Zafar; Ayman A Saeyeldin; Adam J Brownstein; Bulat A Ziganshin; John A Elefteriades; Sandip K Mukherjee Journal: Ann Cardiothorac Surg Date: 2017-11
Authors: E Martínez-Martínez; M Miana; R Jurado-López; M V Bartolomé; F V Souza Neto; M Salaices; N López-Andrés; V Cachofeiro Journal: Int J Obes (Lond) Date: 2014-03-03 Impact factor: 5.095
Authors: Brendan Doyle; Paul Sorajja; Brian Hynes; Arun H S Kumar; Phillip A Araoz; Paul G Stalboerger; Dylan Miller; Cynthia Reed; Jeffrey Schmeckpeper; Shaohua Wang; Chunsheng Liu; Andre Terzic; David Kruger; Stephen Riederer; Noel M Caplice Journal: Stem Cells Dev Date: 2008-10 Impact factor: 3.272