These findings suggest that NecroX-5 may act as a mitochondrial Ca(2+) uniporter inhibitor to protect cardiac mitochondria against HR damage.

The purpose of the study was to assess the effects of a 12 weeks aged garlic extract (AGE) regimen with regular exercise on cardiovascular disease (CVD) risk in postmenopausal women. A total of 30 postmenopausal women (54.4 ± 5.4 years) were randomly divided into the following four groups: Placebo (Placebo; n = 6), AGE intake (AGEI; n = 8), exercise and placebo (Ex + Placebo; n = 8), exercise and AGE (Ex + AGE; n = 8) groups. The AGE group consume 80 mg per day, and exercise groups performed moderate exercise (aerobic and resistance) three times per week. After 12 weeks of treatment, body composition, lipid profile, and CVD risk factors were analyzed. Body weight was significantly decreased in AGEI, Ex + Placebo, and Ex + AGE groups compared to baseline. Body fat % was significantly decreased in the AGEI and Ex + Placebo groups. Body mass index (BMI) was significantly decreased in the AGEI, Ex + Placebo, and Ex + AGE groups. Fat-free mass was significantly decreased in the AGEI group. Total cholesterol (TC) was significantly lower in the Ex + Placebo compared to the Placebo group. AGE supplementation or exercise effectively reduced low-density lipoprotein (LDL-C). Triglyceride (TG) was significantly increased in the AGEI group. Malondialdehyde (MDA) levels were significantly decreased in the AGEI, Ex + Placebo, and Ex + AGE compared to the placebo group. AGE supplementation reduced homocysteine levels regardless of whether the women also exercised. The present results suggest that AGE supplementation reduces cardiovascular risk factors independently of exercise in postmenopausal women.

Increasing evidence suggests that circulating angiogenic cells (CACs) promote repair of ischemic tissues. Activation of formyl peptide receptor 2 (Fpr2) has been reported to stimulate repair of ischemic heart. This study was conducted to investigate the role of Fpr2 on CAC mobilization and cardiac protection in myocardial infarction (MI). WKYMVm, a strong agonist for Fpr2, was administered in a murine model of acute MI, and mobilization of CACs including endothelial progenitor cells (CD34 Flk1 or Sca1 Flk1 cells) in peripheral blood was monitored. CAC mobilization by daily injection of WKYMVm for the first 4 days after MI was as efficient as granulocyte colony-stimulating factor and provided myocardial protection from apoptosis with increased vascular density and preservation of cardiac function. Transplantation of bone marrow (BM) from green fluorescent protein mice showed that BM-derived cells homed to ischemic heart after WKYMVm treatment and contributed to tissue protection. Transplantation of BM from Fpr2 knockout mice showed that Fpr2 in BM cells is critical in mediation of WKYMVm-stimulated myocardial protection and neovascularization after MI. These results suggest that activation of Fpr2 in BM after WKYMVm treatment provides cardiac protection through mobilization of CACs after MI, which may lead to the development of a new clinical protocol for treating patients with ischemic heart conditions. Stem Cells 2017;35:654-665.

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that has been linked to autosomal recessive non-syndromic mental retardation. Several key findings suggest diverse roles of CRBN, including its regulation of the large-conductance calcium- and voltage-activated potassium (BKCa) channels, regulation of thalidomide-binding proteins, and mediation of lenalidomide treatment in multiple myeloma. Recent studies also indicate that CRBN is involved in energy metabolism and negatively regulates AMP-activated protein kinase signaling. Mice with genetic depletion of CRBN are resistant to various stress conditions including a high-fat diet, endoplasmic reticulum stress, ischemia/reperfusion injury, and alcohol-related liver damage. In this review, we discuss the various roles of CRBN in human health and disease and suggest avenues for further research to enhance our basic knowledge and clinical application of CRBN.

Echinochrome A (Ech A), a marine bio-product isolated from sea urchin eggs, is known to have cardioprotective effects through its strong antioxidant and ATP-sparing capabilities. However, the effects of Ech A on cardiac excitation-contraction (E-C) are not known. In this study, we investigated the effects of Ech A on cardiac contractility and Ca(2+) handling in the rat heart. In ex vivo Langendorff hearts, Ech A (3 μM) decreased left ventricular developing pressure to 77.7 ± 6.5 % of basal level. In isolated ventricular myocytes, Ech A reduced the fractional cell shortening from 3.4 % at baseline to 2.1 %. Ech A increased both diastolic and peak systolic intracellular Ca(2+) ([Ca(2+)]i). However, the ratio of peak [Ca]i to resting [Ca]i was significantly decreased. Ech A did not affect the L-type Ca(2+) current. Inhibiting the Na(+)/Ca(2+) exchanger with either NiCl2 or SEA400 did not affect the Ech A-dependent changes in Ca(2+) handling. Our data demonstrate that treatment with Ech A results in a significant reduction in the phosphorylation of phospholamban at both serine 16 and threonine 17 leading to a significant inhibition of SR Ca(2+)-ATPase 2A (SERCA2A) and subsequent reduced Ca(2+) uptake into the intracellular Ca(2+) store. Taken together, our data show that Ech A negatively regulates cardiac contractility by inhibiting SERCA2A activity, which leads to a reduction in internal Ca(2+) stores.