Kevin M Casin

Bio: Kevin M Casin is an academic researcher from Emory University. The author has contributed to research in topics: Cardiomyopathy & Cardioprotection. The author has an hindex of 1, co-authored 2 publications receiving 5 citations.

Harnessing the Benefits of Endogenous Hydrogen Sulfide to Reduce Cardiovascular Disease.

Abstract: Cardiovascular disease is the leading cause of death in the U.S. While various studies have shown the beneficial impact of exogenous hydrogen sulfide (H2S)-releasing drugs, few have demonstrated the influence of endogenous H2S production. Modulating the predominant enzymatic sources of H2S-cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase-is an emerging and promising research area. This review frames the discussion of harnessing endogenous H2S within the context of a non-ischemic form of cardiomyopathy, termed diabetic cardiomyopathy, and heart failure. Also, we examine the current literature around therapeutic interventions, such as intermittent fasting and exercise, that stimulate H2S production.

Dynamic Regulation of Cysteine Oxidation and Phosphorylation in Myocardial Ischemia-Reperfusion Injury.

Abstract: Myocardial ischemia-reperfusion (I/R) injury significantly alters heart function following infarct and increases the risk of heart failure. Many studies have sought to preserve irreplaceable myocardium, termed cardioprotection, but few, if any, treatments have yielded a substantial reduction in clinical I/R injury. More research is needed to fully understand the molecular pathways that govern cardioprotection. Redox mechanisms, specifically cysteine oxidations, are acute and key regulators of molecular signaling cascades mediated by kinases. Here, we review the role of reactive oxygen species in modifying cysteine residues and how these modifications affect kinase function to impact cardioprotection. This exciting area of research may provide novel insight into mechanisms and likely lead to new treatments for I/R injury.

Physiological roles of hydrogen sulfide in mammalian cells, tissues and organs.

Abstract: H2S belongs to the class of molecules known as gasotransmitters, which also includes nitric oxide (NO) and carbon monoxide (CO). Three enzymes are recognized as endogenous sources of H2S in various cells and tissues: cystathionine g-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). The current article reviews the regulation of these enzymes as well as the pathways of their enzymatic and non-enzymatic degradation and elimination. The multiple interactions of H2S with other labile endogenous molecules (e.g. NO) and reactive oxygen species are also outlined. The various biological targets and signaling pathways are discussed, with special reference to H2S and oxidative posttranscriptional modification of proteins, the effect of H2S on channels and intracellular second messenger pathways, the regulation of gene transcription and translation and the regulation of cellular bioenergetics and metabolism. The pharmacological and molecular tools currently available to study H2S physiology are also reviewed, including their utility and limitations. In subsequent sections, the role of H2S in the regulation of various physiological and cellular functions is reviewed. The physiological role of H2S in various cell types and organ systems are overviewed. Finally, the role of H2S in the regulation of various organ functions is discussed as well as the characteristic bell-shaped biphasic effects of H2S. In addition, key pathophysiological aspects, debated areas, and future research and translational areas are identified A wide array of significant roles of H2S in the physiological regulation of all organ functions emerges from this review.

Sulfide regulation of cardiovascular function in health and disease

Abstract: Hydrogen sulfide (H2S) has emerged as a gaseous signalling molecule with crucial implications for cardiovascular health. H2S is involved in many biological functions, including interactions with nitric oxide, activation of molecular signalling cascades, post-translational modifications and redox regulation. Various preclinical and clinical studies have shown that H2S and its synthesizing enzymes — cystathionine γ-lyase, cystathionine β-synthase and 3-mercaptosulfotransferase — can protect against cardiovascular pathologies, including arrhythmias, atherosclerosis, heart failure, myocardial infarction and ischaemia–reperfusion injury. The bioavailability of H2S and its metabolites, such as hydropersulfides and polysulfides, is substantially reduced in cardiovascular disease and has been associated with single-nucleotide polymorphisms in H2S synthesis enzymes. In this Review, we highlight the role of H2S, its synthesizing enzymes and metabolites, their roles in the cardiovascular system, and their involvement in cardiovascular disease and associated pathologies. We also discuss the latest clinical findings from the field and outline areas for future study. Hydrogen sulfide (H2S) is a gaseous signalling molecule with important roles in cardiovascular health and disease. In this Review, Kevil and colleagues discuss the role of H2S, its synthesizing enzymes and metabolites, their roles in the cardiovascular system, and their involvement in cardiovascular disease and associated pathologies.

The Impact of H2S on Obesity-Associated Metabolic Disturbances

Abstract: Over the last several decades, hydrogen sulfide (H2S) has gained attention as a new signaling molecule, with extensive physiological and pathophysiological roles in human disorders affecting vascular biology, immune functions, cellular survival, metabolism, longevity, development, and stress resistance. Apart from its known functions in oxidative stress and inflammation, new evidence has emerged revealing that H2S carries out physiological functions by targeting proteins, enzymes, and transcription factors through a post-translational modification known as persulfidation. This review article provides a critical overview of the current state of the literature addressing the role of H2S in obesity-associated metabolic disturbances, with particular emphasis on its mechanisms of action in obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases.

Biosynthesis, Quantification and Genetic Diseases of the Smallest Signaling Thiol Metabolite: Hydrogen Sulfide

Abstract: Hydrogen sulfide (H2S) is a gasotransmitter and the smallest signaling thiol metabolite with important roles in human health. The turnover of H2S in humans is mainly governed by enzymes of sulfur amino acid metabolism and also by the microbiome. As is the case with other small signaling molecules, disease-promoting effects of H2S largely depend on its concentration and compartmentalization. Genetic defects that impair the biogenesis and catabolism of H2S have been described; however, a gap in knowledge remains concerning physiological steady-state concentrations of H2S and their direct clinical implications. The small size and considerable reactivity of H2S renders its quantification in biological samples an experimental challenge. A compilation of methods currently employed to quantify H2S in biological specimens is provided in this review. Substantial discrepancy exists in the concentrations of H2S determined by different techniques. Available methodologies permit end-point measurement of H2S concentration, yet no definitive protocol exists for the continuous, real-time measurement of H2S produced by its enzymatic sources. We present a summary of available animal models, monogenic diseases that impair H2S metabolism in humans including structure-function relationships of pathogenic mutations, and discuss possible approaches to overcome current limitations of study.