VEGF-C and aortic cardiomyocytes guide coronary artery stem development

Chen, Heidi I.; Poduri, Aruna; Numi, Harri J.; Kivelä, Riikka; Saharinen, Pipsa; McKay, Andrew; Raftrey, Brian; Churko, Jared M.; Tian, Xueying; Zhou, Bin; Wu, Joseph C.; Alitalo, Kari; Red-Horse, Kristy

doi:10.1172/jci77483

Cited by 116 publications

(152 citation statements)

References 66 publications

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“…Strains used were wild type (CD1 and FVB, Charles River Laboratories), ApjCreER (see below), Nfatc1Cre (Wu et al, 2012), Sema3dCre (Katz et al, 2012), Vegfc-lacZ (Karkkainen et al, 2004), Vegfr3-lacZ (Dumont et al, 1998), Vegfc flox (Chen et al, 2014), Dach1 (Davis et al, 2001), Rosa mTmG Cre reporter (The Jackson Laboratory) and Gt(ROSA)26Sor tm4(ACTB-tdTomato,-EGFP)Luo , Rosa tdTomato Cre reporter (The Jackson Laboratory). ApjCreER was created through recombineering (Sharan et al, 2009;Warming et al, 2005).…”

Section: Micementioning

confidence: 99%

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis

et al. 2014

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Identifying coronary artery progenitors and their developmental pathways could inspire novel regenerative treatments for heart disease. Multiple sources of coronary vessels have been proposed, including the sinus venosus (SV), endocardium and proepicardium, but their relative contributions to the coronary circulation and the molecular mechanisms regulating their development are poorly understood. We created an ApjCreER mouse line as a lineagetracing tool to map SV-derived vessels onto the heart and compared the resulting lineage pattern with endocardial and proepicardial contributions to the coronary circulation. The data showed a striking compartmentalization to coronary development. ApjCreER-traced vessels contributed to a large number of arteries, capillaries and veins on the dorsal and lateral sides of the heart. By contrast, untraced vessels predominated in the midline of the ventral aspect and ventricular septum, which are vessel populations primarily derived from the endocardium. The proepicardium gave rise to a smaller fraction of vessels spaced relatively uniformly throughout the ventricular walls. Dorsal (SV-derived) and ventral (endocardialderived) coronary vessels developed in response to different growth signals. The absence of VEGFC, which is expressed in the epicardium, dramatically inhibited dorsal and lateral coronary growth but left vessels on the ventral side unaffected. We propose that complementary SV-derived and endocardial-derived migratory routes unite to form the coronary vasculature and that the former requires VEGFC, revealing its role as a tissue-specific mediator of blood endothelial development.

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Section: Micementioning

confidence: 99%

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis

et al. 2014

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“…56 Recent studies demonstrated that VEGFC is an important regulator of coronary vasculature development, and it would be of great interest to determine whether this function relates to beneficial effects of VEGFC in a mouse model of MI. 189,190 The roles of lymphatic vessels in MI and atherosclerosis are summarized in Figure 5. It is clear that much further analysis is needed to dissect the role of the lymphatic vessels in the pathogenesis of cardiovascular disease including dietary fat absorption and metabolism, adipose tissue inflammation, obesity, RCT, regulation of tissue inflammation, and innate and adaptive immunity.…”

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confidence: 99%

Lymphatic System in Cardiovascular Medicine

Aspelund

Robciuc

Karaman³

et al. 2016

Circulation Research

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Abstract:The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

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“…Studies of the avian and mammalian yolk sac have shown that blood flow is required for plexus remodeling (Lucitti et al 2007). Arterial remodeling in the heart's coronary plexus directly follows initiation of blood flow and does not occur in mutants where the coronary artery does not connect to its blood flow source, the aorta (Chen et al 2014a;Ivins et al 2015;Volz et al 2015). Live imaging of the yolk sac and regenerating zebrafish fins revealed that arterial remodeling involves vessel fusion and endothelial migration against blood flow, toward the growing artery (Sato et al 2010;Udan et al 2013;Xu et al 2014).…”

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DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12–CXCR4 signaling axis

et al. 2017

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Sufficient blood flow to tissues relies on arterial blood vessels, but the mechanisms regulating their development are poorly understood. Many arteries, including coronary arteries of the heart, form through remodeling of an immature vascular plexus in a process triggered and shaped by blood flow. However, little is known about how cues from fluid shear stress are translated into responses that pattern artery development. Here, we show that mice lacking endothelial Dach1 had small coronary arteries, decreased endothelial cell polarization, and reduced expression of the chemokine Cxcl12. Under shear stress in culture, Dach1 overexpression stimulated endothelial cell polarization and migration against flow, which was reversed upon CXCL12/CXCR4 inhibition. In vivo, DACH1 was expressed during early arteriogenesis but was down in mature arteries. Mature artery-type shear stress (high, uniform laminar) specifically down-regulated DACH1, while the remodeling artery-type flow (low, variable) maintained DACH1 expression. Together, our data support a model in which DACH1 stimulates coronary artery growth by activating Cxcl12 expression and endothelial cell migration against blood flow into developing arteries. This activity is suppressed once arteries reach a mature morphology and acquire high, laminar flow that down-regulates DACH1. Thus, we identified a mechanism by which blood flow quality balances artery growth and maturation.

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VEGF-C and aortic cardiomyocytes guide coronary artery stem development

Cited by 116 publications

References 66 publications

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis

Lymphatic System in Cardiovascular Medicine

DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12–CXCR4 signaling axis

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