thymosin and Cardiovascular-Diseases

Since clinical revascularization techniques of coronary or peripheral artery disease (CAD/PAD) focus on macrovessels of the heart, the microcirculatory compartment largely goes unnoticed. However, cardiovascular risk factors not only drive large vessel atherosclerosis, but also microcirculatory rarefaction, an instance unmet by current therapeutic schemes. Angiogenic gene therapy has the potential to reverse capillary rarefaction, but only if the disease-causing inflammation and vessel-destabilization are addressed. This review summarizes the current knowledge with regard to capillary rarefaction due to cardiovascular risk factors. Moreover, the potential of Thymosin ß4 (Tß4) and its downstream signal, myocardin-related transcription factor-A (MRTF-A), to counteract capillary rarefaction are discussed.

Topics: Cardiovascular Diseases; Coronary Artery Disease; Heart Disease Risk Factors; Humans; Microcirculation; Microvascular Rarefaction; Risk Factors; Thymosin

The last 20 years witnessed the emergence of the thymosin β4 (Tβ4)-

Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Humans; Oligopeptides; Thymosin

Formation of the vasculature is a complex process, defects in which can lead to embryonic lethality or disease in later life. Understanding mechanisms of vasculogenesis may facilitate the treatment of developmental defects and may be extrapolated to promote wound healing and tissue repair. Thymosin β4 (Tβ4) is an actin monomer binding protein with recognized roles in vascular development, neovascularization and protection against disease.. Vascular network assembly is complex, regulated by multiple signals and cell types; Tβ4 functions in many of the underlying processes, including vasculogenesis, angiogenesis, arteriogenesis, endothelial-mesenchymal transition and extracellular matrix remodeling. Loss of Tβ4 perturbs vessel growth and stability, whereas exogenous application enhances capillary formation and pericyte recruitment, during development and in injury models.. Although vascular functions for Tβ4 have been well documented, the underlying molecular mechanisms remain obscure. While Tβ4-induced cytoskeletal remodeling likely mediates the directional migration of endothelial cells, paracrine roles have also been implicated in migration and differentiation of smooth muscle cells. Moreover, nuclear functions of Tβ4 have been described but remain to be explored in the vasculature. Delineati+ng the molecular pathways impacted by Tβ4 to promote vascular growth and remodeling may reveal novel targets for prevention and treatment of vascular disease.

Topics: Animals; Blood Vessels; Cardiovascular Diseases; Cell Differentiation; Cytoprotection; Endothelial Cells; Extracellular Matrix; Humans; Myocytes, Smooth Muscle; Neovascularization, Physiologic; Thymosin; Wound Healing

The burden of cardiovascular disease is a growing worldwide issue that demands attention. While many clinical trials are ongoing to test therapies for treating the heart after myocardial infarction (MI) and heart failure, there are few options doctors able to currently give patients to repair the heart. This eventually leads to decreased ventricular contractility and increased systemic disease, including vascular disorders that could result in stroke. Small peptides such as thymosin β4 (Tβ4) are upregulated in the cardiovascular niche during fetal development and after injuries such as MI, providing increased neovasculogenesis and paracrine signals for endogenous stem cell recruitment to aid in wound repair. New research is looking into the effects of in vivo administration of Tβ4 through injections and coatings on implants, as well as its effect on cell differentiation. Results so far demonstrate Tβ4 administration leads to robust increases in angiogenesis and wound healing in the heart after MI and the brain after stroke, and can differentiate adult stem cells toward the cardiac lineage for implantation to the heart to increase contractility and survival. Future work, some of which is currently in clinical trials, will demonstrate the in vivo effect of these therapies on human patients, with the goal of helping the millions of people worldwide affected by cardiovascular disease.

Topics: Cardiovascular Diseases; Cardiovascular System; Cell Differentiation; Humans; Myocardial Infarction; Stroke; Thymosin; Tissue Scaffolds

The Fourth International Symposium on Thymosins in Health and Disease brought together many of the leading scientists, clinicians and thought-leaders from the United States, Israel, Europe, China and Japan to discuss the latest advances and clinical applications of the thymosins in both basic and clinical areas. The symposium, held in Rome, Italy, on October 23 - 25, 2014, was sponsored by The George Washington University and the University of Rome 'Tor Vergata.'

Topics: Animals; Cardiovascular Diseases; Europe; Health Status; HIV Infections; Humans; Internationality; Rome; Thymosin