Vascular dysfunction in HFpEF: Potential role in the development, maintenance, and progression of the disease

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a complex, heterogeneous disease characterized by autonomic imbalance, cardiac remodeling, and diastolic dysfunction. One feature that has recently been linked to the pathology is the presence of macrovascular and microvascular dysfunction. Indeed, vascular dysfunction directly affects the functionality of cardiomyocytes, leading to decreased dilatation capacity and increased cell rigidity, which are the outcomes of the progressive decline in myocardial function. The presence of an inflammatory condition in HFpEF produced by an increase in proinflammatory molecules and activation of immune cells (i.e., chronic low-grade inflammation) has been proposed to play a pivotal role in vascular remodeling and endothelial cell death, which may ultimately lead to increased arterial elastance, decreased myocardium perfusion, and decreased oxygen supply to the tissue. Despite this, the precise mechanism linking low-grade inflammation to vascular alterations in the setting of HFpEF is not completely known. However, the enhanced sympathetic vasomotor tone in HFpEF, which may result from inflammatory activation of the sympathetic nervous system, could contribute to orchestrate vascular dysfunction in the setting of HFpEF due to the exquisite sympathetic innervation of both the macro and microvasculature. Accordingly, the present brief review aims to discuss the main mechanisms that may be involved in the macro- and microvascular function impairment in HFpEF and the potential role of the sympathetic nervous system in vascular dysfunction.

Effects of Electronic Cigarette Vaping on Cardiac and Vascular Function, and Post-myocardial Infarction Remodeling in Rats

“…Consistent with these studies, our present results also support that chronic E-cig exposure impaired the vascular function in the post-MI healing phase in rats. Note that in our experimental myocardial infarction model, post-MI pathophysiological conditions itself can induce vascular dysfunction [ 20 ]. The underlying mechanism may involve the decrease in the bioavailability of NO, accumulation of ROS, chronic low-grade inflammation, and enhanced sympathetic vasomotor tone, and needs to be further investigated.…”

Unraveling the Complexity: From Molecular Subtypes to Therapeutic Strategies in Heart Failure with Preserved Ejection Fraction and Atrial Fibrillation

“…These impact molecular pathways including the renin-angiotensin-aldosterone system and nitric oxide signaling. [12][13][14]. Apart from that, RAAS and nitric oxide signaling are also the part of the development and perpetuation of AF [15].…”

“…Similar to AF, HFpEF is associated with heightened sympathetic activity, which contributes to vasoconstriction, increased afterload, and myocardial fibrosis [56,71]. The mutual feedback amongst the SNS overactivation and the RAAS activation provides a setting for the adverse ventricular remodeling [72]. The sympathetic stimulation causes a production of sympathetic impulse by the brain, which results in sympathoexcitation in HFpEF [73].…”

Obesity, Preserved Ejection Fraction Heart Failure, and Left Ventricular Remodeling

“…The contribution of endothelium-independent and endothelium-dependent vasodilatation to CMD ranges from balanced to mostly endothelium-independent in HFpEF [124,[128][129][130]. Further, in addition to functional microvascular derangements, coronary microvascular rarefaction reduces myocardial O 2 delivery in HFpEF [131].…”