Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

Abstract

Endothelial cells (ECs) constitute the innermost layer in all blood vessels to maintain the structural integrity and microcirculation function for coronary microvasculature. Impaired endothelial function is demonstrated in various cardiovascular diseases including myocardial infarction (MI), which is featured by reduced myocardial blood flow as a result of epicardial coronary obstruction, thrombogenesis, and inflammation. In this context, understanding the cellular and molecular mechanisms governing the function of coronary ECs is essential for the early diagnosis and optimal treatment of MI. Although ECs contain relatively fewer mitochondria compared with cardiomyocytes, they function as key sensors of environmental and cellular stress, in the regulation of EC viability, structural integrity and function. Mitochondrial quality control (MQC) machineries respond to a broad array of stress stimuli to regulate fission, fusion, mitophagy and biogenesis in mitochondria. Impaired MQC is a cardinal feature of EC injury and dysfunction. Hence, medications modulating MQC mechanisms are considered as promising novel therapeutic options in MI. Here in this review, we provide updated insights into the key role of MQC mechanisms in coronary ECs and microvascular dysfunction in MI. We also discussed the option of MQC as a novel therapeutic target to delay, reverse or repair coronary microvascular damage in MI. Contemporary available MQC-targeted therapies with potential clinical benefits to alleviate coronary microvascular injury during MI are also summarized.

RETRACTED: Mitofusin-2 Enhances Mitochondrial Contact With the Endoplasmic Reticulum and Promotes Diabetic Cardiomyopathy

“…Greater mitochondria–ER contact during hyperglycemia promoted the release of calcium from the ER to the mitochondria, resulting in mitochondrial calcium overload, an early event in mitochondrial dysfunction. Excessive mitochondrial calcium disrupted mitochondrial metabolism and inhibited mitochondrial ATP production by interrupting the citric acid cycle ( Chang et al, 2021 ; Zhu et al, 2021 ). Enhanced mitochondria–ER contact was followed by an increased mitochondrial ROS production, an indicator of mitochondrial oxidative stress.…”

RETRACTED: Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction

“…Mitochondrial division depends on the cooperation between mitochondrial fission factors and the endoplasmic reticulum (ER) ( Chang et al, 2021 ; Zhu and Zhou, 2021 ). The ER provides anchoring strength to promote mitochondrial contraction, while mitochondrial fission factors such as mitochondrial fission 1 (Fis1), dynamin-related protein 1 (Drp1), mitochondrial fission factor (Mff), mitochondrial dynamics protein of 49 kDa (Mid49) and mitochondrial dynamics protein of 51 kDa (Mid51) perform the contraction ( Zhou et al, 2018b ; Lobo-Gonzalez et al, 2020 ).…”

Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury

“…Next, mitophagy is employed as a scavenger to eliminate structurally compromised mitochondria [ 25 , 66 ]. As mitophagy-mediated mitochondrial removal is usually followed by a decline in the number of mitochondria, mitochondrial biogenesis is always activated by mitophagy to complement the population and reinforce ATP synthesis [ 67 , 68 ]. Therefore, UPR mt and mitophagy can be considered as distinct mitochondrial repair pathways; the former controlling mitochondrial proteomics and the latter modifying the mitochondrial number.…”