Abstract-The present study examined whether nestin ϩ neural-like stem cells detected in the scar tissue of rats 1 week after myocardial infarction (MI) were derived from bone marrow and/or were resident cells of the normal myocardium. Irradiated male Wistar rats transplanted with -actin promoter-driven, green fluorescent protein (GFP)-labeled, unfractionated bone marrow cells were subjected to coronary artery ligation. Three weeks after MI, GFP-labeled bone marrow cells were detected in the infarct region, and a modest number were associated with nestin immunoreactivity. The paucity of GFP ϩ /nestin ϩ cells in the scar tissue provided the impetus to explore whether neural-like stem cells were derived from cardiac tissue. Nestin mRNA and immunoreactivity were detected in normal rat myocardium, and transcript levels were increased in the damaged heart after MI. In primary-passage, cardiac tissue-derived neural cells, filamentous nestin staining was associated with a diffuse, cytoplasmic glial fibrillary acidic protein signal. Unexpectedly, in viable myocardium, numerous nestin ϩ /glial fibrillary acidic protein ϩ fiberlike structures of varying length were detected and observed in close proximity to neurofilament-M ϩ fibers. The infarct region was likewise innervated, and the preponderance of neurofilament-M ϩ fibers appeared to be physically associated with nestin ϩ fiberlike structures. These data highlight the novel observation that the normal rat heart contained resident nestin ϩ /glial fibrillary acidic protein ϩ neural-like stem cells, fiberlike structures, and nestin mRNA levels that were increased in response to myocardial ischemia. Cardiac tissue-derived neural stem cell migration to the infarct region and concomitant nestin
It remains presently unknown whether vascular reactivity is impaired and whether maladaptive cardiac remodeling occurs before the onset of overt obesity and in the absence of hyperlipidemia. Normal female rats were fed a high-fat diet for 8 weeks and were associated with a modest nonsignificant increase of body weight (standard diet, 300 Ϯ 10, versus high-fat diet, 329 Ϯ 14 g) and a normal plasma lipid profile. In rats fed a high-fat diet, systolic (171 Ϯ 7 mm Hg) and diastolic blood pressures (109 Ϯ 3) were increased compared to a standard diet (systolic blood pressure, 134 Ϯ 8; diastolic blood pressure, 96 Ϯ 5 mm Hg), and acetylcholine-dependent relaxation of isolated aortic rings (high-fat diet, 22 Ϯ 5%, versus standard diet, 53 Ϯ 8%) was significantly reduced. Furthermore, perivascular fibrosis was detected in the heart of rats fed a high-fat diet. The exogenous addition of resveratrol (trans-3,5,4Ј-trihydroxystilbene) (0.1 M) to aortic rings isolated from rats fed a high-fat diet restored acetylcholine-mediated relaxation (47 Ϯ 9%). The administration of resveratrol (20 mg/kg/day for 8 weeks) to rats fed a high-fat diet prevented the increase in blood pressure and preserved acetylcholine-dependent relaxation of isolated aortic rings. However, resveratrol therapy failed to attenuate the perivascular fibrotic response. These data have demonstrated that a high-fat diet fed to normal female rats can elicit a hypertensive response and induce perivascular fibrosis before the development of overt obesity and in the absence of hyperlipidemia. Resveratrol therapy can prevent the hypertensive response in female rats fed a high-fat diet but is without effect on the progression of perivascular fibrosis.
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