Microvascular Rarefaction in the Sinoatrial Node: A Potential Mechanism for Pacemaker Dysfunction in Early HFpEF

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Vascular Biology

Background:

• Microvascular rarefaction is a hallmark of heart failure with preserved ejection fraction (HFpEF).
• The role of Angiotensin II (AngII) signaling in sinoatrial (SA) node dysfunction, a common complication of HFpEF, is not well understood.

Purpose of the Study:

• To investigate whether alterations in SA node microvascular architecture contribute to pacemaker dysfunction in early-stage HFpEF.

Main Methods:

• Mice were infused with a sub-pressor dose of AngII for 28 days.
• SA node structure and function were assessed using electrocardiography, echocardiography, confocal imaging, spatial RNA detection, and optical mapping.

Main Results:

• AngII infusion led to progressive bradycardia and increased beat-to-beat heart rate variability in both male and female mice.
• A significant reduction in microvessel density was observed in the superior SA node, correlating with impaired heart rate regulation.
• Up-regulation of oxidative stress and hypoxia-inducible factor 1α and vascular endothelial growth factor signaling pathways was noted.

Conclusions:

• Microvascular rarefaction in the superior SA node is an early pathological event in HFpEF.
• Compromised vascular architecture impairs metabolic support for pacemaking, leading to SA node dysfunction.
• Rarefaction can negatively impact excitability in metabolically demanding tissues.