Elucidating molecular mechanisms that alleviate cardiac microvascular dysfunction in diabetes: The potential benefit of targeting mitophagy and mitochondrial integrity.

MITOCHONDRIAL pathology; HEART diseases; HEART failure; MICROCIRCULATION disorders; MITOCHONDRIA; AMINO acid derivatives; CORONARY disease

Their investigation demonstrated that 24 weeks of LC treatment (dosed at 200 mg/kg/day) in I db/db i mice: (1) improved cardiac function by upregulating glucose and lipid metabolism and (2) improved cardiac microvascular perfusion by enhancing endothelium-dependent vasodilation. In this issue of I Acta Physiologica i , Li et al. report that L-carnitine (LC) therapy reversed mitochondrial dysfunction and repaired cardiac microvascular injury in diabetic cardiomyopathy.[1] Specifically, they describe how LC augmented PINK1-Parkin-dependent mitophagy by maintaining the PHB2-PARL interaction via CPT1 in I db/db i mice.[1] This is an interesting discovery that holds translational value given the growing recognition of mitophagy as a contributing factor to coronary microvascular dysfunction (CMD).[2] Mitophagy is an autophagic response that specifically targets damaged and, therefore, potentially cytotoxic mitochondria.[3] Interestingly, a recent in vitro study of human umbilical vein endothelial cells reported that mitophagy alleviated ischemia/reperfusion-induced microvascular damage by improving mitochondrial quality control,[4] suggesting that mitophagy may represent a key quality control pathway in the microcirculation. LC treatment subsequently alleviates this dysfunction by enhancing the PHB2-PARL interaction (via CPT1a activation), resulting in enhanced mitophagy and cardiac microvascular protection. [Extracted from the article]

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