Endogenously produced hydrogen sulfide (H₂S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H₂S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H₂S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H₂O₂ increased the levels of H₂S, H₂S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative stress. SG-1002 also decreased the expression of hypertrophic/HF protein markers such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), galectin-3, TIMP1, collagen type III, and TGF-β1 in stressed HL-1 cells. Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated without or with H₂O₂. Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing H₂S levels or H₂S producing enzymes, CBS, and antioxidant proteins.

• Malaria parasites manipulate the mammalian immune response to facilitate survival. • Parasites dampen cytotoxic/antiparasitic responses by inducing Th2-type responses. • In addition to promoting survival, Th2 responses alter transmission to mosquitoes. • Concomitant bacteremia with malaria infection may be a product of this manipulation.

Human immunodeficiency virus (HIV) attacks the immune system and weakens the ability to fight infections/disease. Furthermore, HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. The pathological mechanisms responsible for the increased incidence of cardiovascular disease in HIV patients are largely unknown. We hypothesized that increased oxidative stress and attenuated circulating levels of the cardioprotective gaseous signaling molecules, nitric oxide (NO), and hydrogen sulfide (H₂S) were involved in the cardiovascular pathobiology observed in HIV patients. Plasma samples from both HIV patients and age–matched normal subjects were used for all assays. Oxidative stress was determined by analyzing the levels of advanced oxidation protein products (AOPP) and H₂O₂. Antioxidant levels were determined by measuring the levels of trolox equivalent capacity. ADMA, hs-CRP, and IL-6 were determined by using ELISA. The levels of H₂S (free H₂S and sulfane sulfur) and NO₂ (nitrite) were determined in the plasma samples by using gas chromatography and HPLC, respectively. In the present study we observed a marked induction in the levels of oxidative stress and decreased antioxidant status in the plasma of HIV patients as compared with the controls. Circulating levels of the cardiovascular disease biomarkers: ADMA, hs-CRP (high-sensitivity C-reactive protein), and IL-6 were significantly increased in the circulatory system of HIV patients. The levels of both nitrite and H₂S/sulfane sulfur were significantly reduced in the plasma of HIV patients as compared with normal subjects. Our data demonstrate significant increases in circulating biomarkers of oxidative stress and cardiovascular (CV) in conjunction with decreased bioavailability of H₂S and NO in HIV patients. Diminished levels of these two cardioprotective gaseous signaling molecules may be involved in the pathogenesis of CV disease in the setting of HIV.