Role of Cardiolipin in regulating and treating atherosclerotic cardiovascular diseases

Cardiovascular diseases, mainly caused by atherosclerosis, are the leading causes of morbidity and mortality worldwide. Despite the discrepancies in clinical manifestations between different abnormalities, atherosclerosis shares similar pathophysiological processes, such as mitochondrial dysfunction. Cardiolipin (CL) is a conserved mitochondria-specific lipid that contributes to the cristae structure of the inner mitochondrial membrane (IMM). Alterations in the CL, including oxidative modification, reduced quantity, and abnormal localization, contribute to the onset and progression of atherosclerosis. In this review, we summarize the knowledge that CL is involved in the pathogenesis of atherosclerosis. On the one hand, CL and its oxidative modification promote the progression of atherosclerosis via several mechanisms, including oxidative stress, apoptosis, and inflammation in response to stress. On the other hand, CL externalizes to the outer mitochondrial membrane (OMM) and acts as the pivotal "eat-me" signal in mitophagy, removing dysfunctional mitochondria and safeguarding against the progression of atherosclerosis. Given the imbalance between proatherogenic and antiatherogenic effects, we provide our understanding of the roles of the CL and its oxidative modification in atherosclerotic cardiovascular diseases, in addition to potential therapeutic strategies aimed at restoring the CL. Briefly, CL is far more than a structural IMM lipid; broader significances of the evolutionarily conserved lipid need to be explored.