Transforming growth factor-β signaling in myogenic cells regulates vascular morphogenesis, differentiation, and matrix synthesis.

Objective: Transforming growth factor-β (TGF-β) signaling is required for normal vascular development. We aimed to discover the role of TGF-β signaling in embryonic smooth muscle cells (SMCs).

Methods And Results: We bred mice with smooth muscle (SM) 22α-Cre and Tgfbr2(flox) alleles to generate embryos in which the type II TGF-β receptor (TGFBR2; required for TGF-β signaling) was deleted in SMCs.

TGF-[beta]1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice.

Objective: Impairment of transforming growth factor (TGF)-beta1 signaling accelerates atherosclerosis in experimental mice. However, it is uncertain whether increased TGF-beta1 expression would retard atherosclerosis. The role of TGF-beta1 in aneurysm formation is also controversial.

The phosphodiesterase-5 inhibitor tadalafil reduces myocardial infarct size.

The aim of this study was to determine, in an animal model, the effects of tadalafil on myocardial infarct size (IS), hemodynamics and regional myocardial blood flow after myocardial ischemia and reperfusion. Patients with erectile dysfunction (ED) often have risk factors for coronary artery disease. Tadalafil, a long-acting inhibitor of the enzyme phosphodiesterase-5 (PDE5), is used for the treatment of ED; there are no previous data regarding tadalafil in the setting of coronary artery occlusion (CAO).

Molecular aspects of ischemic heart disease: ischemia/reperfusion-induced genetic changes and potential applications of gene and RNA interference therapy.

Molecular biologic techniques have a variety of applications in the study of ischemic heart disease, including roles in elucidating cardiac genetic changes resulting from ischemia as well as in developing therapeutic interventions to treat ischemic heart disease. This review describes recent studies documenting genetic changes associated with myocardial ischemia and infarction as well as those investigating the safety and effectiveness of gene therapy for stimulating angiogenesis, protecting the heart against reperfusion injury, and treating heart failure. Also discussed are future research directions, including the potential use of RNA interference and combined stem cell therapy and gene therapy for the treatment of cardiovascular disease.

Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces myocardial infarct size without affecting hemodynamics.

Mildronate is a fatty acid oxidation inhibitor approved as an antianginal drug in parts of Europe. We carried out the first study to determine whether a 10-day course of mildronate could reduce myocardial infarct size (IS) during acute myocardial ischemia. Sprague Dawley rats received 200 mg/kg/d of mildronate (treated group, n = 16) or sterile water (control group, n = 14) subcutaneously for 10 days before ischemia-reperfusion.