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Recent studies have revealed the existence of multipotent nestin-immunoreactive cells in the adult mammalian heart. These cells were recruited to infarct site following ischemic injury and differentiated to a vascular lineage leading to de novo blood vessel formation. Here, we show that a sub-population of cardiac resident nestin cells can further differentiate to a neuronal-like fate in vivo following myocardial infarction. In the ischemically damaged rat heart, neurofilament-M fibres were detected innervating the peri-infarct/infarct region and the preponderance of these fibres were physically associated with processes emanating from nestin cells. One week after isogenic heterotopic cardiac transplantation, the beating transplanted rat heart was devoid of neurofilament-M fibre staining. The superimposition of an ischemic insult to the transplanted heart led to the de novo synthesis of neurofilament-M fibres by cardiac resident nestin cells. Nerve growth factor infusion and the exposure of normal rats to intermittent hypoxia significantly increased the density of neurofilament-M fibres in the heart. However, these newly formed neurofilament-M fibres were not physically associated with nestin processes. These data highlight a novel paradigm of reparative fibrosis as a subpopulation of cardiac resident nestin cells directly contributed to neural remodelling of the peri-infarct/infarct region of the ischemically damaged rat heart via the de novo synthesis of neurofilament-M fibres. J. Cell. Physiol. 226: 1157-1165, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Angiopoietin like-2 (angptl2), a proinflammatory protein, is overexpressed in endothelial cells (ECs) from patients with coronary artery disease (CAD). Whether angptl2 contributes to atherogenesis is unknown. We tested the hypothesis that angptl2 promotes inflammation and leukocyte adhesion onto ECs, thereby accelerating atherogenesis in preatherosclerotic dyslipidemic mice., Methods and Results: In ECs freshly isolated from the aorta, basal expression of TNF-α and IL-6 mRNA was higher in 3-month-old severely dyslipidemic mice (LDLr(-/-); hApoB100(+/+) [ATX]) than in control healthy wild-type (WT) mice (P<0.05) and was increased in both groups by exogenous angptl2 (100 nmol/L). Angptl2 stimulated the adhesion of leukocytes ex vivo on the native aortic endothelium of ATX, but not WT mice, in association with higher expression of ICAM-1 and P-selectin in ECs (P<0.05). Antibodies against these endothelial adhesion molecules prevented leukocyte adhesion. Intravenous administration of angptl2 for 1 month in preatherosclerotic 3-month-old ATX mice increased (P<0.05) total cholesterol and LDL-cholesterol levels, strongly induced (P<0.05) the expression of endothelial proinflammatory cytokines and adhesion molecules while accelerating atherosclerotic lesion formation by 10-fold (P<0.05). Plasma and aortic tissue levels of angptl2 increased (P<0.05) with age and were higher in 6- and 12-month-old ATX mice than in age-matched WT mice. Angptl2 accumulated to high levels in the atherosclerotic lesions (P<0.05). Finally, angptl2 was greatly expressed (P<0.05) in ECs cultured from CAD patients, and circulating angptl2 levels were 6-fold higher in CAD patients compared with age-matched healthy volunteers., Conclusions: Angptl2 contributes to the pathogenesis of atherosclerosis.