Thyroid Hormone, Mitochondrial Function and Cardioprotection

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Existing therapies provide symptomatic and clinical benefit but do not fully address the molecular abnormalities that affect the injured cardiomyocytes. Alterations in mitochondrial function are increasingly recognized to play a key pathogenic role in acute myocardial infarction and in chronic CVD. Mitochondrial dysfunctions in CVD include impaired electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. Recent understanding of the complex interaction between thyroid hormone signaling and microRNAs in the regulation of mitochondria quality control and cell fate can provide novel insights and therapeutic targets. The purpose of this chapter is to illustrate the cardioprotective effects of TH against the exasperation of CVD such as ischemia/reperfusion injury and heart failure, focusing on mitochondrial function and quality control. To this aim, we summarize the main tasks that mitochondria manage in cardiovascular physiology and disease and provide insight into how a myocardial low T3 state may contribute to mitochondrial defects and fibrosis/death axis leading to CVD progression. The beneficial effects of a TH replacement therapy on key mitochondrial pathways implicated in CVD are also discussed.