Disparity in the Under-Utilization of Novel P2Y12 Inhibitors in ST-Elevation Myocardial Infarction Following Percutaneous Coronary Intervention.

Background: The most recent guidelines (European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA)) all favor prasugrel/ticagrelor over clopidogrel in the setting of acute coronary syndrome (ACS). We therefore sought to investigate which P2Y12 inhibitors were being prescribed in our community hospital setting upon discharge among patients undergoing percutaneous coronary intervention (PCI) in the setting of ST-elevation myocardial infarction (STEMI).

Methods: We identified patients presenting to two Metro Detroit Michigan hospitals with STEMI between January 1, 2018, to December 31, 2021 using the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) PCI registry.

Role of DJ-1 in Modulating Glycative Stress in Heart Failure.

Background DJ-1 is a ubiquitously expressed protein typically associated with the development of early onset Parkinson disease. Recent data suggest that it also plays a role in the cellular response to stress. Here, we sought to determine the role DJ-1 plays in the development of heart failure.

Impact of Lymphangiogenesis on Cardiac Remodeling After Ischemia and Reperfusion Injury.

Background Lymphatic vessels interconnect with blood vessels to form an elaborate system that aids in the control of tissue pressure and edema formation. Although the lymphatic system has been known to exist in a heart, little is known about the role the cardiac lymphatic system plays in the development of heart failure. Methods and Results Mice (C57 BL /6J, male, 8 to 12 weeks of age) were subjected to either myocardial ischemia or myocardial ischemia and reperfusion for up to 28 days.

Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK.

Background: Hydrogen sulfide (HS) is an important regulator of mitochondrial bioenergetics, but its role in regulating mitochondrial biogenesis is not well understood. Using both genetic and pharmacological approaches, we sought to determine if HS levels directly influenced cardiac mitochondrial content.

Results: Mice deficient in the HS-producing enzyme, cystathionine γ-lyase (CSE KO) displayed diminished cardiac mitochondrial content when compared to wild-type hearts.

Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ.

Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation.

DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission.

Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarction and worsened left ventricular function when compared to WT mice, confirming a protective role for DJ-1 in the heart.

Sodium Sulfide Attenuates Ischemic-Induced Heart Failure by Enhancing Proteasomal Function in an Nrf2-Dependent Manner.

Background: Therapeutic strategies aimed at increasing hydrogen sulfide (H2S) levels exert cytoprotective effects in various models of cardiovascular injury. However, the underlying mechanism(s) responsible for this protection remain to be fully elucidated. Nuclear factor E2-related factor 2 (Nrf2) is a cellular target of H2S and facilitator of H2S-mediated cardioprotection after acute myocardial infarction.

Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the suppression of endoplasmic reticulum stress.

Diabetic cardiomyopathy is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. However, the underlying molecular mechanisms that lead to its development have not been fully elucidated. Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that is critical for the regulation of cardiovascular homeostasis.

Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway.

Background: Coronary artery disease remains the principal cause of death in patients with diabetes mellitus. Diabetic mice display exacerbated injury following myocardial ischemia-reperfusion (MI/R) and are resistant to most therapeutic interventions. We have reported that sodium sulfide (Na2S) therapy confers cardioprotection during MI/R in non-diabetic mice.

Nitrite therapy improves left ventricular function during heart failure via restoration of nitric oxide-mediated cytoprotective signaling.

Rationale: Nitric oxide (NO) bioavailability is reduced in the setting of heart failure. Nitrite (NO2) is a critically important NO intermediate that is metabolized to NO during pathological states. We have previously demonstrated that sodium nitrite ameliorates acute myocardial ischemia/reperfusion injury.

Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent.

Previous studies have demonstrated that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H2S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H2S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury.

Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia-reperfusion.

The infarct sparing effects of exercise are evident following both long-term and short-term training regimens. Here we compared the infarct-lowering effects of nitrite therapy, voluntary exercise, and the combination of both following myocardial ischemia-reperfusion (MI/R) injury. We also compared the degree to which each strategy increased cardiac nitrite levels, as well as the effects of each strategy on the nitrite reductase activity of the heart.

Hydrogen sulfide preconditions the db/db diabetic mouse heart against ischemia-reperfusion injury by activating Nrf2 signaling in an Erk-dependent manner.

Hydrogen sulfide (H2S) therapy protects nondiabetic animals in various models of myocardial injury, including acute myocardial infarction and heart failure. Here, we sought to examine whether H2S therapy provides cardioprotection in the setting of type 2 diabetes. H2S therapy in the form of sodium sulfide (Na2S) beginning 24 h or 7 days before myocardial ischemia significantly decreased myocardial injury in db/db diabetic mice (12 wk of age).

H₂S protects against pressure overload-induced heart failure via upregulation of endothelial nitric oxide synthase.

Background: Cystathionine γ-lyase (CSE) produces H2S via enzymatic conversion of L-cysteine and plays a critical role in cardiovascular homeostasis. We investigated the effects of genetic modulation of CSE and exogenous H2S therapy in the setting of pressure overload-induced heart failure.

Methods And Results: Transverse aortic constriction was performed in wild-type, CSE knockout, and cardiac-specific CSE transgenic mice.

Thioredoxin 1 is essential for sodium sulfide-mediated cardioprotection in the setting of heart failure.

Objective: The aim of this study was to determine whether thioredoxin 1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H2S) in a model of ischemic-induced heart failure (HF).

Approach And Results: Mice with a cardiac-specific overexpression of a dominant negative mutant of Trx1 and wild-type littermates were subjected to ischemic-induced HF. Treatment with H2S as sodium sulfide (Na2S) not only increased the gene and protein expression of Trx1 in the absence of ischemia but also augmented the HF-induced increase in both.

Exercise protects against myocardial ischemia-reperfusion injury via stimulation of β(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols.

Rationale: Exercise training confers sustainable protection against ischemia-reperfusion injury in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise protects the heart, but it is apparent that endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) play a role.

Objective: To determine the role of β(3)-adrenergic receptors (β(3)-ARs), eNOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of exercise.

Genetic and pharmacologic hydrogen sulfide therapy attenuates ischemia-induced heart failure in mice.

Background: Hydrogen sulfide (H(2)S) is an endogenous signaling molecule with potent cytoprotective effects. The present study evaluated the therapeutic potential of H(2)S in murine models of heart failure.

Methods And Results: Heart failure was induced by subjecting mice either to permanent ligation of the left coronary artery for 4 weeks or to 60 minutes of left coronary artery occlusion followed by reperfusion for 4 weeks.

Hydrogen sulfide and ischemia-reperfusion injury.

Gasotransmitters are lipid soluble, endogenously produced gaseous signaling molecules that freely permeate the plasma membrane of a cell to directly activate intracellular targets, thus alleviating the need for membrane-bound receptors. The gasotransmitter family consists of three members: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H(2)S). H(2)S is the latest gasotransmitter to be identified and characterized and like the other members of the gasotransmitter family, H(2)S was historically considered to be a toxic gas and an environmental/occupational hazard.