Epicardial and coronary vascular development

ESC CardioMed ◽  
2018 ◽  
pp. 52-56
Author(s):  
Thomas J. Cahill ◽  
Paul R. Riley

The coronary circulation is essential for human life. In embryonic development, abnormal formation of the coronary vasculature can cause death in utero or after birth. In adulthood, atherosclerosis of the coronary arteries is the commonest cause of death worldwide. The last decade has witnessed significant strides forward in our understanding of coronary development. Multiple sources of coronary endothelial cells have been identified using genetic tools for fate mapping. The epicardium, the outermost layer of the developing heart, has emerged as both a source of cell progenitors and key signalling mediators. Knowledge of the specific genes underlying formation, function, and heterogeneity of the epicardium is expanding. Significant challenges remain, however, in understanding the spatiotemporal signalling patterns required for organized migration, differentiation, and patterning of the vasculature. In addition, dissecting how coronary development is perturbed in patients with congenital coronary anomalies is a major ongoing focus of research.

ESC CardioMed ◽  
2018 ◽  
pp. 52-56
Author(s):  
Thomas J. Cahill ◽  
Paul R. Riley

The coronary circulation is essential for human life. In embryonic development, abnormal formation of the coronary vasculature can cause death in utero or after birth. In adulthood, atherosclerosis of the coronary arteries is the commonest cause of death worldwide. The last decade has witnessed significant strides forward in our understanding of coronary development. Multiple sources of coronary endothelial cells have been identified using genetic tools for fate mapping. The epicardium, the outermost layer of the developing heart, has emerged as both a source of cell progenitors and key signalling mediators. Knowledge of the specific genes underlying formation, function, and heterogeneity of the epicardium is expanding. Significant challenges remain, however, in understanding the spatiotemporal signalling patterns required for organized migration, differentiation, and patterning of the vasculature. In addition, dissecting how coronary development is perturbed in patients with congenital coronary anomalies is a major ongoing focus of research.


Author(s):  
Thomas J. Cahill ◽  
Paul R. Riley

The coronary circulation is essential for human life. In embryonic development, abnormal formation of the coronary vasculature can cause death in utero or after birth. In adulthood, atherosclerosis of the coronary arteries is the commonest cause of death worldwide. The last decade has witnessed significant strides forward in our understanding of coronary development. Multiple sources of coronary endothelial cells have been identified using genetic tools for fate mapping. The epicardium, the outermost layer of the developing heart, has emerged as both a source of cell progenitors and key signalling mediators. Knowledge of the specific genes underlying formation, function, and heterogeneity of the epicardium is expanding. Significant challenges remain, however, in understanding the spatiotemporal signalling patterns required for organized migration, differentiation, and patterning of the vasculature. In addition, dissecting how coronary development is perturbed in patients with congenital coronary anomalies is a major ongoing focus of research.


2002 ◽  
Vol 283 (5) ◽  
pp. H1785-H1794 ◽  
Author(s):  
David X. Zhang ◽  
Fu-Xian Yi ◽  
Ai-Ping Zou ◽  
Pin-Lan Li

The present study tested the hypothesis that ceramide, a sphingomylinase metabolite, serves as an second messenger for tumor necrosis factor-α (TNF-α) to stimulate superoxide production, thereby decreasing endothelium-dependent vasorelaxation in coronary arteries. In isolated bovine small coronary arteries, TNF-α (1 ng/ml) markedly attenuated vasodilator responses to bradykinin and A-23187. In the presence of N G-nitro-l-arginine methyl ester, TNF-α produced no further inhibition on the vasorelaxation induced by these vasodilators. With the use of 4,5-diaminofluorescein diacetate fluorescence imaging analysis, bradykinin was found to increase nitric oxide (NO) concentrations in the endothelium of isolated bovine small coronary arteries, which was inhibited by TNF-α. Pretreatment of the arteries with desipramine (10 μM), an inhibitor of acidic sphingomyelinase, tiron (1 mM), a superoxide scavenger, and polyethylene glycol-superoxide dismutase (100 U/ml) largely restored the inhibitory effect of TNF-α on bradykinin- and A-23187-induced vasorelaxation. In addition, TNF-α activated acidic sphingomyelinase and increased ceramide levels in coronary endothelial cells. We conclude that TNF-α inhibits NO-mediated endothelium-dependent vasorelaxation in small coronary arteries via sphingomyelinase activation and consequent superoxide production in endothelial cells.


Author(s):  
Susan Gallogly ◽  
Takeshi Fujisawa ◽  
John D. Hung ◽  
Mairi Brittan ◽  
Elizabeth M. Skinner ◽  
...  

Abstract Purpose Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. Methods In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. Results CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. Conclusions CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes.


2014 ◽  
Vol 92 (4) ◽  
pp. 338-349 ◽  
Author(s):  
Kiranj K. Chaudagar ◽  
Anita A. Mehta

Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia–reperfusion and (ii) rats hearts that underwent ischemia–reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia–reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS–NO release.


2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.


Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1801-1809 ◽  
Author(s):  
Yoshihiro Yamada ◽  
Yuichi Oike ◽  
Hisao Ogawa ◽  
Yasuhiro Ito ◽  
Hajime Fujisawa ◽  
...  

Neuropilin-1 (NP-1) is a receptor for vascular endothelial growth factor-165 (VEGF165) and acts as a coreceptor that enhances the function of VEGF165 through VEGF receptor-2 (VEGFR-2). Studies using transgenic and knock-out mice of NP-1 indicated that this molecule is important for vascular development as well as neuronal development. We recently reported that clustered soluble NP-1 phosphorylates VEGFR-2 on endothelial cells with a low dose of VEGF165 and rescues the defective vascularity of the NP-1−/− embryo in vitro and in vivo. Here we show that NP-1 is expressed by CD45+ hematopoietic cells in the fetal liver, can bind VEGF165, and phosphorylates VEGFR-2 on endothelial cells. CD45+NP-1+ cells rescued the defective vasculogenesis and angiogenesis in the NP-1−/− P-Sp (para-aortic splanchnopleural mesodermal region) culture, although CD45+NP-1− cells did not. Moreover, CD45+NP-1+ cells together with VEGF165 induced angiogenesis in an in vivo Matrigel assay and cornea neovascularization assay. The extracellular domain of NP-1 consists of “a,” “b,” and “c” domains, and it is known that the “a” and “c” domains are necessary for dimerization of NP-1. We found that both the “a” and “c” domains are essential for such rescue of defective vascularities in the NP-1 mutant. These results suggest that NP-1 enhances vasculogenesis and angiogenesis exogenously and that dimerization of NP-1 is important for enhancing vascular development. In NP-1−/− embryos, vascular sprouting is impaired at the central nervous system (CNS) and pericardium where VEGF is not abundant, indicating that NP-1–expressing cells are required for normal vascular development.


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