David J. Polhemus
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View article: Low Dose GLP-1 Therapy Attenuates Pathological Cardiac and Hepatic Remodelling in HFpEF Independent of Weight Loss
Low Dose GLP-1 Therapy Attenuates Pathological Cardiac and Hepatic Remodelling in HFpEF Independent of Weight Loss Open
BACKGROUND AND AIMS Heart failure with preserved ejection fraction (HFpEF) remains a therapeutic challenge. GLP-1 receptor agonists (GLP-1RAs) show clinical promise, and the prevailing hypothesis is that their benefits are primarily driven…
View article: Vericiguat prevents high glucose-mediated impaired vascular smooth muscle cGMP production and vasorelaxation
Vericiguat prevents high glucose-mediated impaired vascular smooth muscle cGMP production and vasorelaxation Open
Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger cyclic guanosine monophosphate (cGMP) leading to in…
View article: VERICIGUAT RESCUES CYCLIC GUANOSINE MONOPHOSPHATE PRODUCTION IN HUMAN AORTIC VASCULAR SMOOTH MUSCLE CELLS AND AUGMENTS VASORELAXATION IN AORTIC RINGS EXPOSED TO HIGH GLUCOSE
VERICIGUAT RESCUES CYCLIC GUANOSINE MONOPHOSPHATE PRODUCTION IN HUMAN AORTIC VASCULAR SMOOTH MUSCLE CELLS AND AUGMENTS VASORELAXATION IN AORTIC RINGS EXPOSED TO HIGH GLUCOSE Open
Background Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger, cyclic guanosine monophosphate (cGMP) l…
View article: Vericiguat rescues cyclic guanosine monophosphate production in human aortic vascular smooth muscle cells and augments vasorelaxation in aortic rings exposed to high glucose
Vericiguat rescues cyclic guanosine monophosphate production in human aortic vascular smooth muscle cells and augments vasorelaxation in aortic rings exposed to high glucose Open
Background:Vascular smooth muscle cell (VSMC) function relies on endothelial derived nitric oxide (NO) to stimulate cyclic guanosine monophosphate (cGMP) production through soluble guanylyl cyclase (sGC), and vasorelaxation. In inflammato…
View article: Combination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a “2‐Hit” Murine Model
Combination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a “2‐Hit” Murine Model Open
Background Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection…
View article: Hydrogen Sulfide as a Potential Therapy for Heart Failure—Past, Present, and Future
Hydrogen Sulfide as a Potential Therapy for Heart Failure—Past, Present, and Future Open
Hydrogen sulfide (H2S) is an endogenous, gaseous signaling molecule that plays a critical role in cardiac and vascular biology. H2S regulates vascular tone and oxidant defenses and exerts cytoprotective effects in the heart and circulation…
View article: Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury
Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury Open
Background Hydrogen sulfide (H 2 S) is an important endogenous physiological signaling molecule and exerts protective properties in the cardiovascular system. Cystathionine γ‐lyase (CSE), 1 of 3 H 2 S producing enzyme, is predominantly loc…
View article: Nonlethal Inhibition of Gut Microbial Trimethylamine N‐oxide Production Improves Cardiac Function and Remodeling in a Murine Model of Heart Failure
Nonlethal Inhibition of Gut Microbial Trimethylamine N‐oxide Production Improves Cardiac Function and Remodeling in a Murine Model of Heart Failure Open
Background Patients at increased risk for coronary artery disease and adverse prognosis during heart failure exhibit increased levels of circulating trimethylamine N‐oxide ( TMAO ), a metabolite formed in the metabolism of dietary phosphat…
View article: Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease
Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease Open
Hydrogen sulfide (H 2 S)—a potent gaseous signaling molecule—has emerged as a critical regulator of cardiovascular homeostasis. H 2 S is produced enzymatically by 3 constitutively active endogenous enzymes in all mammalian species. Within …
View article: Combined Angiotensin Receptor–Neprilysin Inhibitors Improve Cardiac and Vascular Function Via Increased NO Bioavailability in Heart Failure
Combined Angiotensin Receptor–Neprilysin Inhibitors Improve Cardiac and Vascular Function Via Increased NO Bioavailability in Heart Failure Open
Background There is a paucity of data about the mechanisms by which sacubitril/valsartan (also known as LCZ696) improves outcomes in patients with heart failure. Specifically, the effects of sacubitril/valsartan on vascular function and NO…
View article: A novel mtDNA repair fusion protein attenuates maladaptive remodeling and preserves cardiac function in heart failure
A novel mtDNA repair fusion protein attenuates maladaptive remodeling and preserves cardiac function in heart failure Open
Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1-III) containing…
View article: Restoration of Hydrogen Sulfide Production in Diabetic Mice Improves Reparative Function of Bone Marrow Cells
Restoration of Hydrogen Sulfide Production in Diabetic Mice Improves Reparative Function of Bone Marrow Cells Open
Background: Bone marrow cell (BMC)–based treatment for critical limb ischemia in diabetic patients yielded a modest therapeutic effect resulting from cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functi…
View article: Zofenopril Protects Against Myocardial Ischemia–Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability
Zofenopril Protects Against Myocardial Ischemia–Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability Open
Background Zofenopril, a sulfhydrylated angiotensin‐converting enzyme inhibitor (ACEI), reduces mortality and morbidity in infarcted patients to a greater extent than do other ACEIs. Zofenopril is a unique ACE I that has been shown to incr…
View article: Radiofrequency Renal Denervation Protects the Ischemic Heart via Inhibition of GRK2 and Increased Nitric Oxide Signaling
Radiofrequency Renal Denervation Protects the Ischemic Heart via Inhibition of GRK2 and Increased Nitric Oxide Signaling Open
Rationale: Catheter-based renal denervation (RDN) is currently under development for the treatment of resistant hypertension and is thought to reduce blood pressure via interruption of sympathetic pathways that modulate cardiovascular func…
View article: PO-20 A HYDROGEN SULFIDE PRODRUG AUGMENTS ANGIOGENESIS IN A SWINE MODEL OF CRITICAL LIMB ISCHEMIA VIA A NITRIC OXIDE DEPENDENT MECHANISM
PO-20 A HYDROGEN SULFIDE PRODRUG AUGMENTS ANGIOGENESIS IN A SWINE MODEL OF CRITICAL LIMB ISCHEMIA VIA A NITRIC OXIDE DEPENDENT MECHANISM Open
Introduction: Despite advances in revascularization, treatments for critical limb ischemia (CLI) have been largely unsuccessful. Hydrogen sulfide (H2S) and nitric oxide (NO), are endogenous gasotransmitters which exert potent vasodilatory …
View article: Choline Diet and Its Gut Microbe–Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload–Induced Heart Failure
Choline Diet and Its Gut Microbe–Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload–Induced Heart Failure Open
Background— Trimethylamine N-oxide (TMAO), a gut microbe–dependent metabolite of dietary choline and other trimethylamine-containing nutrients, is both elevated in the circulation of patients having heart failure and heralds worse overall …
View article: Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol
Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol Open
Endothelial dysfunction is more prevalent in African Americans ( AAs ) compared with whites. The authors hypothesized that nebivolol, a selective β 1 ‐antagonist that stimulates nitric oxide ( NO ), will improve endothelial function in AAs…
View article: Analysis of erectile responses to H<sub>2</sub>S donors in the anesthetized rat
Analysis of erectile responses to H<sub>2</sub>S donors in the anesthetized rat Open
Hydrogen sulfide (H 2 S) is a biologically active endogenous gasotransmitter formed in penile tissue that has been shown to relax isolated cavernosal smooth muscle. In the present study, erectile responses to the H 2 S donors sodium sulfid…
View article: Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease
Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease Open
Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathol…
View article: Hydrogen Sulfide Levels and Nuclear Factor‐Erythroid 2‐Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI)
Hydrogen Sulfide Levels and Nuclear Factor‐Erythroid 2‐Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI) Open
Background Cystathionine γ‐lyase, cystathionine β‐synthase, and 3‐mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen sulfide (H 2 S). Functions of H 2 S are mediated by several targets including ion channels an…
View article: A Novel Hydrogen Sulfide Prodrug, <scp>SG</scp>1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
A Novel Hydrogen Sulfide Prodrug, <span>SG</span>1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients Open
Summary Recent studies demonstrate robust molecular cross talk and signaling between hydrogen sulfide (H 2 S) and nitric oxide ( NO ). Heart failure ( HF ) patients are deficient in both H 2 S and NO , two molecules that are critical for c…
View article: Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome
Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome Open
Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, includ…