scholarly journals Molecular Dysfunction and Phenotypic Derangement in Diabetic Cardiomyopathy

2019 ◽  
Vol 20 (13) ◽  
pp. 3264 ◽  
Author(s):  
Isabella Evangelista ◽  
Ranuccio Nuti ◽  
Tommaso Picchioni ◽  
Francesco Dotta ◽  
Alberto Palazzuoli
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Interstitial Fibrosis ◽  
Vascular Inflammation ◽  
Structural Abnormalities ◽  
Diabetic Population ◽  
Cardio Vascular ◽  
Mitochondrial Networks ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15–20% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described.

scholarly journals Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Natural Antioxidants ◽  
Sirtuin 1 ◽  
Potential Benefits ◽  
New Perspective ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.

scholarly journals Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ERα knockout mice: role of aromatase

2007 ◽  
Vol 293 (3) ◽  
pp. R1239-R1246 ◽  
Author(s):  
Dong Sun ◽  
Changdong Yan ◽  
Azita Jacobson ◽  
Houli Jiang ◽  
Mairead A. Carroll ◽  
...  
Keyword(s):  
Gas Chromatography Mass Spectrometry ◽  
Epoxyeicosatrienoic Acids ◽  
Epoxyeicosatrienoic Acid ◽  
Wild Type ◽  
Electrophysiological Technique ◽  
Isolated Arteries ◽  
Oxide Synthase ◽  
Interfering Rna ◽  
Endothelial Nitric Oxide

We studied the roles of estrogen receptors (ER) and aromatase in the mediation of flow-induced dilation (FID) in isolated arteries of male ERα-knockout (ERα-KO) and wild-type (WT) mice. FID was comparable between gracilis arteries of WT and ERα-KO mice. In WT arteries, inhibition of NO and prostaglandins eliminated FID. In ERα-KO arteries, Nω-nitro-l-arginine methyl ester (l-NAME) inhibited FID by ∼26%, whereas indomethacin inhibited dilations by ∼50%. The remaining portion of the dilation was abolished by additional administration of 6-(2-proparglyoxyphenyl)hexanoic acid (PPOH) or iberiotoxin, inhibitors of epoxyeicosatrienoic acid (EET) synthesis and large-conductance potassium channels, respectively. By using an electrophysiological technique, we found that, in the presence of 10 dyne/cm2 shear stress, perfusate passing through donor vessels isolated from gracilis muscle of ERα-KO mice subjected to l-NAME and indomethacin elicited smooth muscle hyperpolarization and a dilator response of endothelium-denuded detector vessels. These responses were prevented by the presence of iberiotoxin in detector or PPOH in donor vessels. Gas chromatography-mass spectrometry (GC-MS) analysis indicated a significant increase in arterial production of EETs in ERα-KO compared with WT mice. Western blot analysis showed a significantly reduced endothelial nitric oxide synthase expression but enhanced expressions of aromatase and ERβ in ERα-KO arteries. Treatment of ERα-KO arteries with specific aromatase short-interfering RNA for 72 h, knocked down the aromatase mRNA and protein associated with elimination of EET-mediation of FID. Thus, FID in male ERα-KO arteries is maintained via an endothelium-derived hyperpolarizing factor/EET-mediated mechanism compensating for reduced NO mediation due, at least in part, to estrogen aromatized from testosterone.

Sign in / Sign up

Export Citation Format

Share Document