With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms at play. Recently, numerous pro-inflammatory cytokines have been linked to several different CVDs, which are now often considered an adversely pro-inflammatory state. These cytokines most notably include interleukin-6 (IL-6),tumor necrosis factor (TNF)α, and the interleukin-1 (IL-1) family, amongst others. Not only does inflammation have intricate and complex interactions with pathophysiological processes such as oxidative stress and calcium mishandling, but it also plays a role in the balance between tissue repair and destruction. In this regard, pre-clinical and clinical evidence has clearly demonstrated the involvement and dynamic nature of pro-inflammatory cytokines in many heart conditions; however, the clinical utility of the findings so far remains unclear. Whether these cytokines can serve as markers or risk predictors of disease states or act as potential therapeutic targets, further extensive research is needed to fully understand the complex network of interactions that these molecules encompass in the context of heart disease. This review will highlight the significant advances in our understanding of the contributions of pro-inflammatory cytokines in CVDs, including ischemic heart disease (atherosclerosis, thrombosis, acute myocardial infarction, and ischemia-reperfusion injury), cardiac remodeling (hypertension, cardiac hypertrophy, cardiac fibrosis, cardiac apoptosis, and heart failure), different cardiomyopathies as well as ventricular arrhythmias and atrial fibrillation. In addition, this article is focused on discussing the shortcomings in both pathological and therapeutic aspects of pro-inflammatory cytokines in CVD that still need to be addressed by future studies.

As an emerging platform technology, metabolomics offers new insights into the pathomechanisms associated with complex disease conditions, including cardiovascular diseases. It also facilitates assessing the risk of developing the disease before its clinical manifestation. For this reason, metabolomics is of growing interest for understanding the pathogenesis of acute coronary syndromes (ACS), finding new biomarkers of ACS, and its associated risk management. Metabolomics-based studies in ACS have already demonstrated immense potential for biomarker discovery and mechanistic insights by identifying metabolomic signatures (e.g., branched-chain amino acids, acylcarnitines, lysophosphatidylcholines) associated with disease progression. Herein, we discuss the various metabolomics approaches and the challenges involved in metabolic profiling, focusing on ACS. Special attention has been paid to the clinical studies of metabolomics and lipidomics in ACS, with an emphasis on ischemia/reperfusion injury.

Hypertension is one of the most common comorbidities in cardiometabolic diseases, affecting nearly one third of adults. As a result, its pathophysiological mechanisms have been studied extensively and are focused around pressure natriuresis, the renin–angiotensin system (RAS), the sympathetic nervous system, oxidative stress, and endothelial dysfunction. Additionally, hypertension secondary to other underlying etiologies also exists. While clinical evidence has clearly shown differences in hypertension development in males and females, relatively little is known about the pathophysiological mechanisms behind these differences. Sex hormones likely play a key role, as they modulate many factors related to hypertension development. In this review, we postulate the potential role for sexually dimorphic fat metabolism in the physiology of hypertension. In brief, estrogen promotes subcutaneous fat deposition over visceral fat and increases in mass via adaptive hyperplasia rather than pathogenic hypertrophy. This adipose tissue subsequently produces anti-inflammatory effects and inhibits metabolic dysfunction-associated fatty liver disease (MAFLD) and RAS activation, ultimately leading to decreased levels of hypertension in pre-menopausal females. On the other hand, androgens and the lack of estrogens promote visceral and ectopic fat deposition, including in the liver, and lead to increased circulating pro-inflammatory cytokines and potentially subsequent RAS activation and hypertension development in males and post-menopausal females. Understanding the sex-specific differences in fat metabolism may provide deeper insights into the patho-mechanisms associated with hypertension and lead to more comprehensive sex-specific care.