Cardiac diastolic dysfunction by cigarette smoking is associated with mitochondrial integrity in the heart.

Cigarette smoking behaviors are harmful and cause one out of ten deaths due to cardiovascular disease. As population sizes grow and number of cigarette smokers increases, it is vital that we understand the mechanisms leading to heart failure in cigarette smokers. We have reported that metabolic regulation of a histone deacetylase, SIRT1, modulates cardiovascular and mitochondrial function under stress. Given this conclusion, we hypothesized that chronic cigarette smoking led to cardiovascular dysfunction via a reduction SIRT1. Mice were randomly organized into smoking or nonsmoking groups, and the smoking group received cigarette smoke exposure for 16 weeks. Following 16-week exposure, diastolic function of the heart was impaired in the smoking group as compared to sham, indicated by a significant increase in E/e'. The electrical function of the heart was also impaired in the smoking group compared to the sham group, indicated by increased PR interval and decreased QTc interval. This diastolic dysfunction was not accompanied by increased fibrosis in mouse hearts, although samples from human chronic smokers indicated increased fibrosis compared to their nonsmoker counterparts. As well as diastolic dysfunction, mitochondria from the 16-week smoking group showed significantly impaired function, evidenced by significant decreases in all parameters measured by the mitochondrial stress test. We further found biochemical evidence of a significantly decreased level of SIRT1 in left ventricles of both mouse and human smoking groups compared to nonsmoking counterparts. Data from this study indicate that decreased SIRT1 levels by cigarette smoking are associated with diastolic dysfunction caused by compromised mitochondrial integrity.

Platelets at the intersection of inflammation and coagulation in the APC-mediated response to myocardial ischemia/reperfusion injury.

Thromboinflammation is a complex pathology associated with inflammation and coagulation. In cases of cardiovascular disease, in particular ischemia-reperfusion injury, thromboinflammation is a common complication. Increased understanding of thromboinflammation depends on an improved concept of the mechanisms of cells and proteins at the axis of coagulation and inflammation. Among these elements are activated protein C and platelets. This review summarizes the complex interactions of activated protein C and platelets regulating thromboinflammation in cardiovascular disease. By unraveling the pathways of platelets and APC in the inflammatory and coagulation cascades, this review summarizes the role of these vital mediators in the development and perpetuation of heart disease and the thromboinflammation-driven complications of cardiovascular disease. Furthermore, this review emphasizes the significance of the counteracting effects of platelets and APC and their combined role in disease states.

Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Metabolic imbalances and pathological stress often contribute to increased mortality. Sestrin2 (Sesn2) is a stress-inducible protein crucial in maintaining cardiac energy and metabolic homeostasis under pathological conditions. Sesn2 is upregulated in response to various stressors, including oxidative stress, hypoxia, and energy depletion, and mediates multiple cellular pathways to enhance antioxidant defenses, promote autophagy, and inhibit inflammation. This review explores the mechanisms through which Sesn2 regulates these pathways, focusing on the AMPK-mTORC1, Sesn2-Nrf2, and HIF1α-Sesn2 pathways, among others. We can identify the potential therapeutic targets for treating CVDs and related metabolic disorders by comprehending these complex mechanisms. Sesn2's unique ability to respond thoroughly to metabolic challenges, oxidative stress, and inflammation makes it a promising prospect for enhancing cardiac health and resilience against pathological stress.

Myeloid Cells in Myocardial Ischemic Injury: The Role of the Macrophage Migration Inhibitory Factor.

Ischemic heart disease, manifesting as myocardial infarction (MI), remains the leading cause of death in the western world. Both ischemia and reperfusion (I/R) cause myocardial injury and result in cardiac inflammatory responses. This sterile inflammation in the myocardium consists of multiple phases, involving cell death, tissue remodeling, healing, and scar formation, modulated by various cytokines, including the macrophage migration inhibitory factor (MIF). Meanwhile, different immune cells participate in these phases, with myeloid cells acting as first responders. They migrate to the injured myocardium and regulate the initial phase of inflammation. The MIF modulates the acute inflammatory response by affecting the metabolic profile and activity of myeloid cells. This review summarizes the role of the MIF in regulating myeloid cell subsets in MI and I/R injury and discusses emerging evidence of metabolism-directed cellular inflammatory responses. Based on the multifaceted role of the MIF affecting myeloid cells in MI or I/R, the MIF can be a therapeutic target to achieve metabolic balance under pathology and alleviate inflammation in the heart.