Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Liu, Yusheng; Huang, Zhiwei; Wang, Lin; Liu, Xinxin; Wang, Yongmei; Zhang, Yun; Zhang, Mei

doi:10.1016/j.jphs.2014.12.007

Cited by 25 publications

(27 citation statements)

References 32 publications

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“…This is in concurrence with previous studies (Zhong et al 2006;Miao et al 2007;Van Linthout et al 2007;Wang et al 2009;Liu et al 2015). Fibrosis, which characterizes DCM, occurs independent of HTN or CAD and may be associated with myocardial hypertrophy (Huang et al 2010;Tarquini et al 2011).…”

Section: Discussionsupporting

confidence: 90%

“…Caspase-3 expression is increased by hyperglycemia-induced myocardial injury (Cai et al 2002), pressure overload-induced LVD (Philipp et al 2004), and in failing hearts (Narula et al 1999;Scheubel et al 2002) where it can induce myofibrillar ultrastructural damage (Condorelli et al 2001). A recent study conducted by Liu et al (2015) has demonstrated that DM upregulates receptor-interacting protein-3 (RIP 3 ), a signal molecule involved in TNF-a-mediated apoptosis. On the other hand, suppression of cardiac apoptosis is reported to improve the cardiac structure and function (Xie et al 2011;Zou and Xie 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The volume fraction (CVF) of the interstitial (matrix) collagen was analyzed semi-quantitatively by Image-Pro Plus 6.0 software (Media Cybernetics, Bethesda, MD) according to previously described (Sun et al 2004;Liu et al 2015). It was calculated as the area occupied by connective tissue divided by the sum of areas occupied by connective tissue and cardiomyocytes, with exclusion of the intramural vessels, perivascular collagen, endocardium and trabeculae.…”

Section: Morphometric Analysismentioning

confidence: 99%

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Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress

Abdel-Hamid

Firgany

2015

J Mol Hist

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Diabetic hazard on the myocardium is a complication of diabetes that intensifies its morbidity and increases its mortality. Therefore, alleviation of diabetic cardiomyopathy (DCM) by a reliable drug remains a matter of interest in experimental research. The aim of this study was to explore the structural alterations in the myocardium induced by atorvastatin (ATOR) in DCM, induced by streptozotocin (STZ), along with the associated changes occurring in apoptosis and oxidative stress markers. Thirty-two rats were divided into four groups; group A (control), group B (non-diabetic, received ATOR, orally, 50 mg/kg daily), group C (DCM, received STZ 70 mg/kg, single i.p. injection) and group D (DCM + ATOR). After 6 weeks, left ventricle (LV) specimens were prepared for histological and immunohistochemical study by hematoxlyin and eosin, Masson`s trichrome, anti-cleaved caspase-3 stains as well as for assays of oxidative stress markers. All data were measured morphometrically and statistically analyzed. The DCM group showed disorganization of the cardiomyocytes, interstitial edema, numerous fibroblasts, significant increases in the collagen volume fraction (p < 0.001), cleaved caspase-3 expression % area (p < 0.001) and, malondialdehyde in blood (p < 0.001), in LV (p < 0.05) compared with DCM + ATOR group. The latter has LV wall thickness, relative heart weight and antioxidant activities nearly similar to the control, independent from ATOR lipid-lowering effect. Therefore, ATOR can preserve myocardial structure in DCM nearly similar to normal. This may be achieved by suppressing apoptosis that parallels the correction of the antioxidant markers, which can be considered as non-lipid lowering benefit of statins.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Morphometric Analysismentioning

confidence: 99%

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Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress

Abdel-Hamid

Firgany

2015

J Mol Hist

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“…Considerable evidence also links the attenuation of DPP4 activity to improvement in ventricular function and reduced systemic and cardiac inflammation (6,(27)(28)(29). Hence, we were surprised to detect increased cardiac expression of mRNA transcripts encoding multiple effectors of the immune response in normoglycemic mice with reduced DPP4 activity.…”

Section: Discussionmentioning

confidence: 95%

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice

et al. 2015

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Dipeptidyl peptidase-4 (DPP4) inhibitors used for the treatment of type 2 diabetes are cardioprotective in preclinical studies; however, some cardiovascular outcome studies revealed increased hospitalization rates for heart failure (HF) among a subset of DPP4 inhibitor–treated subjects with diabetes. We evaluated cardiovascular function in young euglycemic Dpp4−/− mice and in older, high fat–fed, diabetic C57BL/6J mice treated with either the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide or the highly selective DPP4 inhibitor MK-0626. We assessed glucose metabolism, ventricular function and remodeling, and cardiac gene expression profiles linked to inflammation and fibrosis after transverse aortic constriction (TAC) surgery, a pressure-volume overload model of HF. Young euglycemic Dpp4−/− mice exhibited a cardioprotective response after TAC surgery or doxorubicin administration, with reduced fibrosis; however, cardiac mRNA analysis revealed increased expression of inflammation-related transcripts. Older, diabetic, high fat–fed mice treated with the GLP-1R agonist liraglutide exhibited preservation of cardiac function. In contrast, diabetic mice treated with MK-0626 exhibited modest cardiac hypertrophy, impairment of cardiac function, and dysregulated expression of genes and proteins controlling inflammation and cardiac fibrosis. These findings provide a model for the analysis of mechanisms linking fibrosis, inflammation, and impaired ventricular function to DPP4 inhibition in preclinical studies.

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“…1,2,5 Various animal models have been used in the study of LVDD, including the mRen2.Lewis rats, 9,10 deoxycorticosterone acetate-hypertensive rats, 30 spontaneously hypertensive rats (SHR), 31 streptozotocin and a high-fat diet-induced diabetic rats and mice, 32,33 lipopolysaccharide-induced high inflammation and LVDD, 34 and aortocaval fistula-induced volume overload model. 35 However, all these animal models are pathological models and may not reflect the biological conditions of LVDD that exist in healthy, aging women after the cessation of ovarian estrogen production.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Middle-aged, Ovariectomized Fischer 344 × Brown Norway Rats

Wang

Alencar

et al. 2016

Journal of Cardiovascular Pharmacology

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The incidence of left ventricular diastolic dysfunction (LVDD) increases in women following menopause, yet the mechanisms are unclear. Because mast cells participate in the pathological processes of various cardiac diseases, we hypothesized that mast cell inhibition would protect against estrogen loss-induced LVDD. The mast cell stabilizer, cromolyn sodium (30 mg/kg/day), or vehicle was administered subcutaneously by osmotic minipump to ovariectomized (OVX) female Fischer344×Brown Norway (F344BN) rats starting at four weeks after surgery. Eight weeks after OVX, systolic blood pressure increased by 20% in OVX vs. sham rats, and this effect was attenuated after four weeks of cromolyn treatment. Also, cromolyn mitigated the adverse reductions in myocardial relaxation (e′) and increases in left ventricle (LV) filling pressures (E/e′), LV mass, wall thicknesses, and interstitial fibrosis from OVX. While cardiac mast cell number was increased after OVX, cardiac chymase activity was not overtly altered by estrogen status and tended to decrease by cromolyn. Contrariwise, Ang II content was greater in hearts of OVX vs. sham rats, and cromolyn attenuated this effect. Taken together, mast cell inhibition with cromolyn attenuates LV remodeling and LVDD in OVX-F344BN rats possibly through actions on the heart level and/or via vasodilatory effects at the vascular level.

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Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Abstract: Sitagliptin might have a myocardial protective effect by inhibiting apoptosis, inflammation, lipid accumulation and myocardial fibrosis in diabetic rats, for a potential role in improving left-ventricular function in diabetes.

Cited by 25 publications

References 32 publications

Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress

Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice

Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Middle-aged, Ovariectomized Fischer 344 × Brown Norway Rats

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