Biomaterial Database

Developmental origin of age-related coronary artery disease. 2015

Ke Wei, and Ramon Díaz-Trelles, and Qiaozhen Liu, and Marta Diez-Cuñado, and Maria-Cecilia Scimia, and Wenqing Cai, and Junko Sawada, and Masanobu Komatsu, and Joseph J Boyle, and Bin Zhou, and Pilar Ruiz-Lozano, and Mark Mercola

Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA 92037, USA.

OBJECTIVE Age and injury cause structural and functional changes in coronary artery smooth muscle cells (caSMCs) that influence the pathogenesis of coronary artery disease. Although paracrine signalling is widely believed to drive phenotypic changes in caSMCs, here we show that developmental origin within the fetal epicardium can have a profound effect as well. RESULTS Fluorescent dye and transgene pulse-labelling techniques in mice revealed that the majority of caSMCs are derived from Wt1(+), Gata5-Cre(+) cells that migrate before E12.5, whereas a minority of cells are derived from a later-emigrating, Wt1(+), Gata5-Cre(-) population. We functionally evaluated the influence of early emigrating cells on coronary artery development and disease by Gata5-Cre excision of Rbpj, which prevents their contribution to coronary artery smooth muscle cells. Ablation of the Gata5-Cre(+) population resulted in coronary arteries consisting solely of Gata5-Cre(-) caSMCs. These coronary arteries appeared normal into early adulthood; however, by 5-8 months of age, they became progressively fibrotic, lost the adventitial outer elastin layer, were dysfunctional and leaky, and animals showed early mortality. CONCLUSIONS Taken together, these data reveal heterogeneity in the fetal epicardium that is linked to coronary artery integrity, and that distortion of the coronaries epicardial origin predisposes to adult onset disease.

UI	MeSH Term	Description	Entries
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010496	Pericardium	A conical fibro-serous sac surrounding the HEART and the roots of the great vessels (AORTA; VENAE CAVAE; PULMONARY ARTERY). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers.	Epicardium,Fibrous Pericardium,Parietal Pericardium,Pericardial Cavity,Pericardial Space,Serous Pericardium,Visceral Pericardium,Cavities, Pericardial,Cavity, Pericardial,Pericardial Cavities,Pericardial Spaces,Pericardium, Fibrous,Pericardium, Parietal,Pericardium, Serous,Pericardium, Visceral,Pericardiums, Fibrous,Pericardiums, Serous,Serous Pericardiums,Space, Pericardial,Spaces, Pericardial
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003324	Coronary Artery Disease	Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.	Arteriosclerosis, Coronary,Atherosclerosis, Coronary,Coronary Arteriosclerosis,Coronary Atherosclerosis,Left Main Coronary Artery Disease,Left Main Coronary Disease,Left Main Disease,Arterioscleroses, Coronary,Artery Disease, Coronary,Artery Diseases, Coronary,Atheroscleroses, Coronary,Coronary Arterioscleroses,Coronary Artery Diseases,Coronary Atheroscleroses,Left Main Diseases
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D032389	Myocytes, Smooth Muscle	Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).	Smooth Muscle Cells,Cell, Smooth Muscle,Cells, Smooth Muscle,Myocyte, Smooth Muscle,Smooth Muscle Cell,Smooth Muscle Myocyte,Smooth Muscle Myocytes