Diastolic function parameters are improved by the addition of simvastatin to enalapril-based treatment in hypertensive individuals

Beck, Adenalva L.S.; Otto, Maria Estefânia Bosco; D’Ávila, Luciana Bartolomei Orru; Netto, Fernando Melo; Armendaris, Marinez Kellermann; Sposito, Andrei C.

doi:10.1016/j.atherosclerosis.2012.03.030

Cited by 14 publications

(11 citation statements)

References 24 publications

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“…Previous studies also reported that RAS inhibition could attenuate cardiac remodeling and heart failure in hypertensive cardiomyopathy (27,28), dilated cardiomyopathy (29,30) and coronary artery disease (31) via inhibition of PKC signaling pathway (26). It was found that the phospho-PKCb2, but not phospho-PKCa and phospho-PKCb1, was significantly up-regulated by 124.4 % (p < 0.01) in DCM, and significantly down-regulated by 30.2 and 50.0 % (p < 0.01) in DCM+LD and DCM+HD, respectively (Fig.…”

Section: Resultsmentioning

confidence: 89%

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Hu¹,

Jiang²

2014

Acta Pharmaceutica

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Dilated cardiomyopathy (DCM) is a multifactorial disease involving cardiac dysfunction and enlargement of one or of both ventricles (1). A number of new anti-heart failure medications, even cytokine therapy (2) or stem cell transplantation (3) have been developed (4) C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg -1 d -1 . After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left ventricular short axis fractional shortening (LVFS), accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover, myocardium sarcoplasmic reticulum Ca 2+ pump (SERCA-2) activity was decreased. The ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly with the down-regulation of SERCA--2a and ryanodine receptor (RyR2) expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT 1 R) and protein kinase C (PKC)b2. The possible underlying mechanism might be the regulation of myocardial AT 1 R-PKCb2-Ca 2+ handling proteins.

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Section: Resultsmentioning

confidence: 89%

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Hu¹,

Jiang²

2014

Acta Pharmaceutica

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“…The mechanism of these effects may be related to suppression of the MVA pathway and downstream GTPase activity (30,31). Some cell culture and animal studies have suggested that statins can prevent the development of cardiac hypertrophy and fibrosis (32)(33)(34)(35), which may reduce ventricular compliance and is a major cause of cardiac diastolic dysfunction (36). A meta-analysis of 11 eligible studies, including 17,985 patients with heart failure with a preserved ejection fraction demonstrated that statin therapy may be associated with improved survival rates in these patients (37).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the mevalonate pathway improves myocardial fibrosis

Shen

Liang

et al. 2021

Exp Ther Med

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The mevalonate (MVA) pathway serves an important role in ventricular remodeling. Targeting the MVA pathway has protective effects against myocardial fibrosis. The present study aimed to investigate the mechanism behind these effects. Primary cultured cardiac fibroblasts from C57BL/6 mice were treated in vitro in 5 groups: i) negative control; ii) angiotensin II (Ang II) model (1x10-5 mol/l); iii) Ang II + rosuvastatin (ROS); iv) Ang II + alendronate (ALE); and v) Ang II + fasudil (FAS). Collagen and crystal violet staining were used to assess morphological changes in cardiac fibroblasts. Reverse transcription quantitative PCR and western blotting were used to analyze the expression of key signaling molecules involved in the MVA pathway. Collagen staining in the ALE, FAS, and ROS groups was weak compared with the Ang II group, while the rate of cell proliferation in the ROS, ALE, and FAS groups was slower compared with that in the Ang II group. In addition, the expression of key signaling molecules in the MVA pathway, including transforming growth factor-β1 (TGF-β1), heat shock protein 47 (HSP47), collagen type I α1 (COL1A1), vascular endothelial growth factor 2 (VEGF2) and fibroblast growth factor 2 (FGF2), was decreased in the FAS and ROS groups compared with the Ang II model. Compared with the Ang II group, 3-Hydroxy-3-Methylglutaryl-CoA reductase (HMGCR) gene expression was significantly lowered in the drug intervention groups, whereas farnesyl pyrophosphate synthase (FDPS) expression was downregulated in the ALE group, but elevated in the FAS and ROS groups. Compared with that in the Ang II group, ras homolog family member A (RhoA) expression was downregulated in the FAS and ROS groups, whilst mevalonate kinase expression was reduced in the ROS group. Protein expression of TGF-β1, COL1A1 and HSP47 were decreased following intervention with each of the three drugs compared with the Ang II group. Overall, rosuvastatin, aledronate and fasudil decreased the proliferation of myocardial fibroblasts and inhibited collagen synthesis. Rosuvastatin had the strongest protective effects against myocardial fibrosis compared with the other drugs tested, suggesting this to be a potential agent for the clinical treatment of cardiovascular disease.

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“…[104][105][106] In randomized controlled trials (RCTs), statins reduced the incidence of new-onset as well as recurrent AF; 107-109 their use is also associated with a decrease in AF-related thromboembolic events. 110,111 At the same time, the use of statins is followed by an improvement in abnormal diastolic filling dynamics [112][113][114] as well as by reduced risk for new-onset HF with the features of HFpEF. 115,116…”

Section: Statinsmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

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Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

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Diastolic function parameters are improved by the addition of simvastatin to enalapril-based treatment in hypertensive individuals

Abstract: The addition of simvastatin to enalapril in hypertensive patients with average cholesterol levels improves parameters of diastolic function independently of changes in blood pressure or cholesterol.

Cited by 14 publications

References 24 publications

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Inhibition of the mevalonate pathway improves myocardial fibrosis

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

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