Mitochondrial DNA (mtDNA) damage is associated with the development of cardiovascular diseases. Cardiac aging plays a central role in cardiovascular diseases. There is accumulating evidence linking cardiac aging to mtDNA damage, including mtDNA mutation and decreased mtDNA copy number. Current wisdom indicates that mtDNA is susceptible to damage by mitochondrial reactive oxygen species (mtROS). This review presents the cellular and molecular mechanisms of cardiac aging, including autophagy, chronic inflammation, mtROS, and mtDNA damage, and the effects of mitochondrial biogenesis and oxidative stress on mtDNA. The importance of nucleoid-associated proteins (Pol γ), nuclear respiratory factors (NRF1 and NRF2), the cGAS-STING pathway, and the mitochondrial biogenesis pathway concerning the development of mtDNA damage during cardiac aging is discussed. Thus, the repair of damaged mtDNA provides a potential clinical target for preventing cardiac aging.

The glycocalyx is a complex polysaccharide-protein layer lining the lumen of vascular endothelial cells. Changes in the structure and function of the glycocalyx promote an inflammatory response in blood vessels and play an important role in the pathogenesis of many vascular diseases (e.g., diabetes, atherosclerosis, and sepsis). Vascular endothelial dysfunction is a hallmark of inflammation-related diseases. Endothelial dysfunction can lead to tissue swelling, chronic inflammation, and thrombosis. Therefore, elimination of endothelial inflammation could be a potential target for the treatment of vascular diseases. This review summarizes the key role of the glycocalyx in the inflammatory process and the possible mechanism by which it alleviates this process by interrupting the cycle of endothelial dysfunction and inflammation. Especially, we highlight the roles of different components of the glycocalyx in modulating the inflammatory process, including components that regulate leukocyte rolling, L-selectin binding, inflammasome activation and the signaling interactions between the glycocalyx components and the vascular cells. We discuss how the glycocalyx interferes with the development of inflammation and the importance of preventing glycocalyx impairment. Finally, drawing on current understanding of the role of the glycocalyx in inflammation, we consider a potential strategy for the treatment of vascular diseases.

Bile acids (BAs), key regulators in the metabolic network, are not only involved in lipid digestion and absorption but also serve as potential therapeutic targets for metabolic disorders. Studies have shown that cardiac dysfunction is associated with abnormal BA metabolic pathways. As ligands for several nuclear receptors and membrane receptors, BAs systematically regulate the homeostasis of metabolism and participate in cardiovascular diseases (CVDs), such as myocardial infarction, diabetic cardiomyopathy, atherosclerosis, arrhythmia, and heart failure. However, the molecular mechanism by which BAs trigger CVDs remains controversial. Therefore, the regulation of BA signal transduction by modulating the synthesis and composition of BAs is an interesting and novel direction for potential therapies for CVDs. Here, we mainly summarized the metabolism of BAs and their role in cardiomyocytes and noncardiomyocytes in CVDs. Moreover, we comprehensively discussed the clinical prospects of BAs in CVDs and analyzed the clinical diagnostic and application value of BAs. The latest development prospects of BAs in the field of new drug development are also prospected. We aimed to elucidate the underlying mechanism of BAs treatment in CVDs, and the relationship between BAs and CVDs may provide new avenues for the prevention and treatment of these diseases.

P2X7 purinergic receptor (P2X7R) has been implicated in several cardiovascular diseases. However, whether it regulates cardiac fibrosis remains elusive. Herein, its involvement in the development of cardiac fibrosis was examined using a transverse aortic constriction (TAC) mice model and cardiac fibroblasts (CFs) hyperstimulated by TGF-β1 for 48 hours. Results showed that TAC and TGF-β1 treatment increased the expression of P2X7R. Silencing of P2X7R expression with siP2X7R ameliorated TGF-β1 effects on fibroblasts activation. Similarly, P2X7R inhibition by Brilliant Blue G (BBG) reduced mRNA and protein levels of profibrosis markers, while the P2X7R agonist BzATP accelerated the TGF-β1-induced CFs activation. Moreover, it was found that TGF-β1-induced CFs activation was mediated by the NLRP3/IL-1β inflammasome pathway. BBG or siP2X7R treatment suppressed NLRP3/IL-1β pathway signaling. In vivo, BBG significantly alleviated TAC-induced cardiac fibrosis, cardiac dysfunction, and NLRP3/IL-1β activation. Collectively, our findings imply that suppressing P2X7R may limit cardiac fibrosis and abnormal activation of CFs.