Angiogênese coronariana como resposta endógena da isquemia miocárdica no adulto

Abstract

The process of angiogenesis involves a complex sequence of stimuli and integrated responses, such as stimulation of endothelial cells (ECs) for their proliferation and migration, stimulation of the extracellular matrix (ECM) for the attraction of pericytes and macrophages, stimulation of smooth muscle cells for their proliferation and migration, and formation of new vascular structures. Angiogenesis is mainly an adaptive response to tissue hypoxia and depends on the accumulation of the hypoxia-inducible factor (HIF-1α) in the ischemic myocardial area, which increases the transcription of the vascular endothelial growth factor (VEGF) and its receptors VEGF-R by the ECs undergoing ischemia. Those steps involve enzymatic mechanisms and plasminogen activator proteases, metalloproteinases (MMP) of the ECM, and kinases that cause proteolytic molecular degradation of the ECM and activation and release of growth factors, such as: basic fibroblast growth factor (bFGF), VEGF, and insulin growth factor-1 (IGF-1). In the intermediate phase, stabilization of the immature neovascular sprout occurs. The final phase is characterized by vascular maturation of the physiological angiogenesis. In conclusion, coronary angiogenesis in adults is fundamentally a paracrine response of the preexisting capillary network under pathophysiological condition of ischemia and inflammation.

Macrophages derived from septic mice modulate nitric oxide synthase and angiogenic mediators in the heart

“…Other authors have mentioned that interstitial inflammatory immuno-infiltrates are present in the ischemic heart disease and in myocardium of LPS-induced sepsis (Cuenca et al, 2006;Lorier et al, 2011). This study suggests that Mps obtained from in vivo LPS-treated mice are able to up-regulate its own production of NO as well as VEGF-A levels, MMP-9 expression and activity and new blood vessel formation in heart tissue.…”

Acupuncture Promotes Angiogenesis after Myocardial Ischemia through H3K9 Acetylation Regulation at VEGF Gene

“…Recruitment of cEPCs, as well as proliferation and survival of endothelial cells and vascular smooth muscle cells were necessary for the formation of vascular sprout and lumen. Usually, the high number or density of these cells is indicative of angiogenesis [14]. Our results showed that promoting angiogenesis in ischemic myocardial tissues could be a possible mechanism of the cardioprotective effects of acupuncture in MI cases.…”

“…Our data indicated a marked increase in VEGF genes expression as a result of EA treatment. Angiogenesis is known as an adaptive response to tissue hypoxia in ischemic myocardial areas, and it is considered a target in treating ischemic diseases, including myocardial ischemia [14], [24]. Acupuncture treatment has also proven to alleviate ischemic symptoms in other types of ischemic diseases via promoting angiogenesis [25], [26].…”

“…Myocardial function relies on sufficient blood supply and the normal capillary/myocardial fiber ratio of 1∶1 (one capillary to one myocardial fiber) in an adult heart. In the case of hypoxia, angiogenesis is triggered by insufficient blood supply [14], [15]. Vascular endothelial growth factor (VEGF), one of angiogenic factors, is involved in all phases of angiogenesis, including generation of angiogenic vascular sprout, stabilization of immature neovascular sprout, and maturation of physiological angiogenesis [14].…”

“…In the case of hypoxia, angiogenesis is triggered by insufficient blood supply [14], [15]. Vascular endothelial growth factor (VEGF), one of angiogenic factors, is involved in all phases of angiogenesis, including generation of angiogenic vascular sprout, stabilization of immature neovascular sprout, and maturation of physiological angiogenesis [14]. In ischemic areas, VEGF expression can increase up to 30 times in a few minutes by the accumulation of hypoxia-inducible factor-1 (HIF-1), which activates VEGF transcription by binding to the hypoxia response element (HRE) on the VEGF promoter [16].…”