最先端研究セミナー

 

 

 

 

Abstract:

We have been studying the role of cytokines and growth factors in the cardiovascular development and vascular remodeling in the cardiovascular diseases. The origin and developmental mechanisms underlying coronary vessels are debated for several decades. We focused on the role of angiopoietin-1 (Ang1) for coronary vessel formation in the developing heart. Cardiomyocyte-specific Ang1 deletion resulted in defective formation of the subepicardial coronary veins, but had no significant effect on the formation of intramyocardial coronary arteries. We found that myocardium-derived Ang1 promotes coronary vein formation presumably by promoting the proliferation, migration and differentiation of immature endothelial cells derived from the sinus venosus.

Pulmonary arterial hypertension (PAH) is an intractable disease which causes stenosis and occlusions specifically in the distal areas of pulmonary arteries. Interleukin-6 (IL-6) is a multifunctional pro-inflammatory cytokine which is elevated in the serum of pulmonary arterial hypertension (PAH) patients. Previous animal experiments and clinical human studies indicate that IL-6 plays a critical role in PAH; however, the molecular mechanisms of IL-6-mediated pathogenesis of PAH have been elusive. We recently identified IL-21 as a novel downstream target of IL-6-signaling in a PAH animal model, murine hypoxia-induced pulmonary hypertension (HPH) model. We found that IL-21 promotes PAH in association with M2 macrophage polarization, downstream of IL-6-signaling. IL-6/IL-21-signaling axis might be a novel potential target for treating refractory PAH.

 

References

1. Arita Y, Nakaoka Y*, et al. Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart. Nat Commun. 2014 Jul 29; 5: 4552.
2. Hashimoto-Kataoka T, Nakaoka Y,* et al. Interleukin-6/interleukin-21-signaling axis is critical in the pathogenesis of pulmonary arterial hypertension. Proc Natl Acad Sci U S A. 2015 May 19; 112(20): E2677-86.
3. Nakaoka Y*, et al. Tocilizumab for the Treatment of the Patients with Refractory Takayasu Arteritis. Int Heart J. 54, 406-411, 2013

 

 

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