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Microvascular Rarefaction and Heart Failure With Preserved Ejection Fraction.

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and is commonly seen in the elderly and diabetic and hypertensive patients. Despite its rising prevalence, the pathophysiology of HFpEF is poorly understood and its optimal treatment remains undefined. Recent clinical studies indicate that coronary microvascular rarefaction (reduced myocardial capillary density) with reduced coronary flow reserve (CFR) is a major contributor to diastolic dysfunction in HFpEF patients. On a molecular level, endothelial cells (EC) are dependent on glycolysis for supporting their functions and vascular homeostasis. Sirtuin 3 (SIRT3) has a critical role in the regulation of endothelial glycolytic metabolism and thus affects angiogenesis. Disruption of SIRT3-mediated EC metabolism and impairment of angiogenesis may promote cardiomyocyte hypoxia and myocardial fibrosis, leading to diastolic dysfunction and HFpEF. This review summarizes current knowledge of SIRT3 in EC metabolism, coronary microvascular rarefaction and HFpEF.

SUBMITTER: Zeng H

PROVIDER: S-EPMC6403466 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Microvascular Rarefaction and Heart Failure With Preserved Ejection Fraction.

Zeng Heng H Chen Jian-Xiong JX

Frontiers in cardiovascular medicine 20190228

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and is commonly seen in the elderly and diabetic and hypertensive patients. Despite its rising prevalence, the pathophysiology of HFpEF is poorly understood and its optimal treatment remains undefined. Recent clinical studies indicate that coronary microvascular rarefaction (reduced myocardial capillary density) with reduced coronary flow reserve (CFR) is a major contributor to diastolic dysfunction ...[more]

PMID: 30873415

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Project description:Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly different from heart failure with reduced EF in terms of etiology and natural history (Graziani et al., 2018). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (Crea et al., 2017). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (Paulus and Tschope, 2013). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (Ohanyan et al., 2018). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (Graziani et al., 2018;Lam et al., 2018). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.

Dataset Information

Microvascular Rarefaction and Heart Failure With Preserved Ejection Fraction.

Publications

Microvascular Rarefaction and Heart Failure With Preserved Ejection Fraction.

Similar Datasets

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