PPubMed14 Dec 2020Cited 25×

Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease Cardiac pericytes are vasoregulators L. L. Lee <i> et al </i> .

Linda L. Lee, Aarif Y. Khakoo, Vishnu Chintalgattu

Abstract

Pericytes (PCs) in general are known to help maintain vessel integrity; however, their specific function in the heart is not well defined. Our in vitro study details NG2+ PDGFRβ+ CD146+ CD34− CD31− CD45− cardiac PC phenotypic and functional characteristics, and their role in vasoregulation in physiological and disease prone environments. Cardiac PCs can potentially regulate blood flow in the heart.

A figure from Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease Cardiac pericytes are vasoregulators L. L. Lee <i> et al </i> . — fig. from the paper

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Cardiac pericytes can contract and relax in response to vasoactive signals, influencing blood flow and disease processes like hypoxia, atherosclerosis, and diabetes.

What’s new

i.Defined the phenotypic marker profile of primary cardiac pericytes (NG2+ PDGFRβ+ CD146+ CD34− CD31− CD45−).
ii.Demonstrated in vitro contractile and relaxation responses of cardiac pericytes to phenylephrine and adenosine using ECIS impedance measurements.
iii.Showed hypoxia activates HIF‑1α, increases PDGF‑bb and VEGF‑A secretion, and leads to cell death between days 3‑4.
iv.Assessed the impact of high LDL and high glucose on pericyte cytokine expression and viability.

How they did it

Primary mouse cardiac pericytes were isolated and characterized by flow cytometry. Their contractile behavior was measured with ECIS impedance assays under phenylephrine, adenosine, LDL, and glucose/insulin treatments, while hypoxic responses were evaluated via western blot, immunocytochemistry, and resazurin viability assays. Gene expression was quantified by qRT-PCR and RNA‑seq.

What they found

Phenylephrine caused a dose‑dependent decrease in impedance (n=6, P=0.0008 to P≤0.0001).
Adenosine induced dose‑dependent impedance increases (n=6, significant at P≤0.0001).
Hypoxia increased nuclear HIF‑1α (P≤0.0001) and protein levels (P=0.0001); cells began dying between days 3‑4.
Hypoxic PCs secreted more PDGF‑bb (P=0.0115) and VEGF‑A (P≤0.0001).
High glucose (50 mM) did not affect proliferation, but low glucose (5.5 mM) caused cell death.
High glucose raised CCL2 mRNA (P=0.01154, 0.02269) and TNF‑α mRNA (P=0.00751, 0.000738); IL‑6 protein decreased (P=0.0064, 0.0359).

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Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease Cardiac pericytes are vasoregulators L. L. Lee <i> et al </i> .

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