Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Vascular Biology

Background:

• Pericytes (PCs) are mural cells supporting endothelial cells (ECs) in microvessels, vital for vasculature development and barrier integrity.
• The specific roles and mechanisms of cardiac PCs in regulating coronary capillary function remain largely uncharacterized.

Purpose of the Study:

• To characterize cardiac pericytes (PCs) at the cellular level and elucidate their function in the heart.
• To investigate the behavior of cardiac PCs under in vitro disease conditions, including hypoxia, hyperlipidemia, and hyperglycemia.

Main Methods:

• Isolation and characterization of cardiac PCs using specific cell surface markers (NG2+, PDGFRβ+, CD146+, CD34-, CD31-, CD45-).
• Functional assays measuring transepithelial electrical resistance and endothelial permeability.
• Assessment of PC contractile protein expression, adrenergic signaling response, and contraction/relaxation.
• In vitro modeling of disease states: hypoxia, supraphysiological low-density lipoprotein (LDL), and elevated glucose.

Main Results:

• Isolated cardiac PCs enhanced endothelial barrier function by increasing transepithelial electrical resistance and decreasing permeability.
• Cardiac PCs express contractile proteins, respond to adrenergic signaling, and exhibit contraction and relaxation.
• Hypoxia induced the HIF-1α pathway, increased angiogenic factor secretion, and promoted PC apoptosis.
• High LDL levels inhibited PC proliferation and induced lipid accumulation, while high glucose triggered a proinflammatory response.

Conclusions:

• Cardiac PCs are vasoactive cells capable of regulating coronary capillary tone and blood flow.
• Cardiac PCs exhibit distinct responses to various in vitro disease stimuli, highlighting their role in cardiovascular pathology.
• This study provides a foundational characterization of cardiac PCs and their functional significance in cardiac health and disease.