Mechanism and potential treatment of the "no reflow" phenomenon after acute myocardial infarction: Role of pericytes and GPR39

Carmen Methner, Zhiping Cao, Anusha Mishra, Sanjiv Kaul

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The "no reflow"phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments, we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, before reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared with controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39- knockout and VC43-treated mice compared with controls. We conclude that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI and that smaller no reflow zones in GPR39-knockout and VC43-treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI, as well as providing a therapeutic pathway for the condition.

Original languageEnglish (US)
Pages (from-to)H1030
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume231
Issue number6
DOIs
StatePublished - Dec 2021

Keywords

  • Acute myocardial infarction
  • GPR39
  • GPR39 antagonist
  • No reflow
  • Pericytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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