Programmed cell death

Cell biology

Mitophagy

Mitochondrial permeability transition pore

Biology

Endothelial stem cell

Angiogenesis

Apoptosis

Autophagy

Ischemia

Cardiology

Biochemistry

Heart failure

In vitro

Oxidative stress

Cardiac function curve

Internal medicine

Mitochondrion

Medicine

Reperfusion injury

Mitochondrial fission

As reperfusion therapies have become more widely used in acute myocardial infarction patients, ischemia-induced myocardial damage has been markedly reduced, but reperfusion-induced cardiac injury has become increasingly evident. The features of cardiac ischemia–reperfusion (I/R) injury include microvascular perfusion defects, platelet activation and sequential cardiomyocyte death due to additional ischemic events at the reperfusion stage. Microvascular obstruction, defined as a no-reflow phenomenon, determines the infarct zone, myocardial function and peri-operative mortality. Cardiac microvascular endothelial cell injury may occur much earlier and with much greater severity than cardiomyocyte injury. Endothelial cells contain fewer mitochondria than other cardiac cells, and several of the pathological alterations during cardiac microvascular I/R injury involve mitochondria, such as increased mitochondrial reactive oxygen species (mROS) levels and disturbed mitochondrial dynamics. Although mROS are necessary physiological second messengers, high mROS levels induce oxidative stress, endothelial senescence and apoptosis. Mitochondrial dynamics, including fission, fusion and mitophagy, determine the shape, distribution, size and function of mitochondria. These adaptive responses modify extracellular signals and orchestrate intracellular processes such as cell proliferation, migration, metabolism, angiogenesis, permeability transition, adhesive molecule expression, endothelial barrier function and anticoagulation. In this review, we discuss the involvement of mROS and mitochondrial morphofunction in cardiac microvascular I/R injury.

New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury