Rationale: The recent emergence of hydrogen sulfide (H ₂ S) as a potent cardioprotective signaling molecule necessitates the elucidation of its cytoprotective mechanisms. Objective: The present study evaluated potential mechanisms of H ₂ S-mediated cardioprotection using an in vivo model of pharmacological preconditioning. Methods and Results: H ₂ S (100 μg/kg) or vehicle was administered to mice via an intravenous injection 24 hours before myocardial ischemia. Treated and untreated mice were then subjected to 45 minutes of myocardial ischemia followed by reperfusion for up to 24 hours, during which time the extent of myocardial infarction was evaluated, circulating troponin I levels were measured, and the degree of oxidative stress was evaluated. In separate studies, myocardial tissue was collected from treated and untreated mice during the early (30 minutes and 2 hours) and late (24 hours) preconditioning periods to evaluate potential cellular targets of H ₂ S. Initial studies revealed that H ₂ S provided profound protection against ischemic injury as evidenced by significant decreases in infarct size, circulating troponin I levels, and oxidative stress. During the early preconditioning period, H ₂ S increased the nuclear localization of Nrf2, a transcription factor that regulates the gene expression of a number of antioxidants and increased the phosphorylation of protein kinase Cε and STAT-3. During the late preconditioning period, H ₂ S increased the expression of antioxidants (heme oxygenase-1 and thioredoxin 1), increased the expression of heat shock protein 90, heat shock protein 70, Bcl-2, Bcl-xL, and cyclooxygenase-2 and also inactivated the proapoptogen Bad. Conclusions: These results reveal that the cardioprotective effects of H ₂ S are mediated in large part by a combination of antioxidant and antiapoptotic signaling.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of disease. This paper discusses the current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes.

Hydrogen sulfide (H2S) is the most recent endogenous gasotransmitter that has been reported to serve many physiological and pathological functions in different tissues. Studies over the past decade have revealed that H2S can be synthesized through numerous pathways and its bioavailability regulated through its conversion into different biochemical forms. H2S exerts its biological effects in various manners including redox regulation of protein and small molecular weight thiols, polysulfides, thiosulfate/sulfite, iron-sulfur cluster proteins, and anti-oxidant properties that affect multiple cellular and molecular responses. However, precise measurement of H2S bioavailability and its associated biochemical and pathophysiological roles remains less well understood. In this review, we discuss recent understanding of H2S chemical biology, its relationship to tissue pathophysiological responses and possible therapeutic uses.

While the opioid epidemic has garnered significant attention, the use of methamphetamines is growing worldwide independent of wealth or region. Following overdose and accidents, the leading cause of death in methamphetamine users is cardiovascular disease, because of significant effects of methamphetamine on vasoconstriction, pulmonary hypertension, atherosclerotic plaque formation, cardiac arrhythmias, and cardiomyopathy. In this review, we examine the current literature on methamphetamine-induced changes in cardiovascular health, discuss the potential mechanisms regulating these varied effects, and highlight our deficiencies in understanding how to treat methamphetamine-associated cardiovascular dysfunction.