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Bazan H.A.,Section of Vascular and Endovascular Surgery | Hatfield S.A.,The New School | O'Malley C.B.,Laboratory of Molecular Cardiology | Brooks A.J.,Section of Vascular and Endovascular Surgery | And 3 more authors.
Stroke | Year: 2015

Background and Purpose-Atherosclerotic plaque vulnerability is accompanied by changes in the molecular and cellular function in the plaque shoulder, including a decrease in vascular smooth muscle cell proliferation. We aimed to determine whether the expression of 3 miRNAs that regulate vascular smooth muscle cell proliferation (miR-145, miR-221, and miR-222) is altered with plaque rupture, suggesting a role in regulating plaque stability. Methods-miRNAs were measured in the plaque shoulder of carotid plaques obtained from patients undergoing carotid endarterectomy (CEA) for 3 distinct clinical scenarios: (1) patients without previous neurological events but high-grade carotid stenosis (asymptomatic), (2) patients with an acute neurological event within 5 days of the CEA (urgent), and (3) patients undergoing CEA>5 days after a neurological event (symptomatic). Results-Mean time from plaque rupture event to CEA was 2.4 days in the urgent group. The urgent group exhibited a significant decrease in miR-221 and miR-222 expression in the plaque shoulder, whereas no significant differences were seen in miR-145 across the 3 groups. Regression analysis demonstrated a significant correlation between time from the neurological event to CEA and increasing miR-221 and miR-222, but not miR-145. mRNA encoding p27Kip1, a target of miR-221 and miR-222 that inhibits vascular smooth muscle cell proliferation, was increased in the urgent group. Conclusions-Atherosclerotic plaque rupture is accompanied by a loss of miR-221 and miR-222 and an increase in p27Kip1 mRNA expression in the plaque shoulder, suggesting an association between these miRNAs and atherosclerotic plaque stability. © 2015 American Heart Association, Inc.

Coleman C.B.,Laboratory of Molecular Cardiology | Coleman C.B.,Tulane University | Lightell D.J.,Laboratory of Molecular Cardiology | Lightell D.J.,Tulane University | And 6 more authors.
Molecular and Cellular Endocrinology | Year: 2013

Diabetes is a major risk factor for cardiovascular disease and is associated with increased intimal thickening and accelerated vascular smooth muscle cell (VSMC) proliferation. We measured the expression of two microRNAs that promote intimal thickening, miR-221/222, and mRNA encoding a downstream target, p27Kip1, in internal mammary artery (IMA) segments collected from 37 subjects undergoing coronary artery bypass grafting. The segments were stratified into three groups: non-diabetic subjects (ND), diabetic subjects not on metformin (DMMet-), and diabetic subjects on metformin (DMMet+). The DMMet- group exhibited a significant increase in miR-221/222 and decrease in p27Kip1 mRNA compared to both the ND and DMMet+ groups. miR-221/222 levels inversely correlated with metformin dose. VSMCs isolated from the IMAs of the DMMet- group proliferate at a faster rate than those of the ND and DMMet+ groups. Further studies into the importance of miR-221/222 in the increased intimal thickening observed in diabetic subjects is warranted. © 2013 Elsevier Ireland Ltd.

Stahls III P.F.,Ochsner Clinic Foundation | Lightell Jr. D.J.,Laboratory of Molecular Cardiology | Moss S.C.,Laboratory of Molecular Cardiology | Goldman C.K.,Ochsner Clinic Foundation | And 3 more authors.
Journal of Cardiovascular Translational Research | Year: 2013

Chronic kidney disease (CKD) is associated with increased coronary artery disease (CAD) and coronary artery calcification. We hypothesized that the osteogenic factor, bone morphogenetic protein-4 (sBMP-4), is elevated in subjects with both CKD and CAD. Serum was collected from 79 subjects undergoing diagnostic angiography and stratified according to CAD and CKD status. Subjects with both CAD and CKD had significantly elevated sBMP-4 compared to those with only one or no disease. sBMP-4 continued to be associated with the presence of both diseases after adjustment for other risk factors. To determine if sBMP-4 is associated with coronary artery calcification, we compared coronary artery calcium scores (CAC) to sBMP-4 in 22 subjects. A positive correlation between CAC and sBMP-4 was seen. In conclusion, sBMP-4 is elevated in patients with both CAD and CKD and positively correlates with CAC, suggesting a role for sBMP-4 in the increased CAD seen in CKD patients. © 2012 Springer Science+Business Media New York.

Latronico M.V.G.,Laboratory of Molecular Cardiology | Condorelli G.,Laboratory of Molecular Cardiology | Condorelli G.,National Research Council Italy
Current Drug Targets | Year: 2010

Heart ion-channel function and expression are continuously being regulated on the basis of the hemodynamic state of the cardiovascular system, the neurohumoral milieu and the properties of the ongoing ionic fluxes. These homeostatic forces act through multiple mechanisms at transcriptional, translational and post-translational levels. Of clinical importance is the fact that with adverse stress these regulatory mechanisms can produce arrhythmogenic channel remodelling. Although a great deal is known about the functionality of ion channels and the generation of the action potential, much less is known about the underlying controlling mechanisms and how these become derailed during disease. microRNA-mediated posttranscriptional control is a very recent addition to cardiovascular biology. Here, we outline discoveries pertaining to these new regulators and how they might be involved in cardiac electrophysiology and pathology. © 2010 Bentham Science Publishers Ltd.

Pecini R.,Copenhagen University | Cedergreen P.,Laboratory of Molecular Cardiology | Theilade S.,Copenhagen University | Haunso S.,Copenhagen University | And 2 more authors.
Europace | Year: 2010

Aims The prevalence of the Brugada-type electrocardiogram (ECG) in the Danish population is not known. Methods and resultsInhabitants from the city of Copenhagen, Denmark, have participated in a prospective study since 1976. Four cross-sectional surveys have been carried out. Follow-up was performed using public registers. At each examination, the participants had an ECG registered. ECGs, showing right bundle branch block (RBBB) were examined for a possible Brugada-type pattern. A total of 42 560 ECGs had been registered from 18 974 participants. 1 284 had been coded as RBBB. Among these ECGs, we found no ECGs showing type 1 Brugada pattern, and 14 showing type 2 or 3 pattern. The prevalence of the total number of ECGs with Brugada pattern was 7/10 000. None of the subjects with a Brugada-pattern ECG died suddenly during follow-up.ConclusionThe Brugada-type ECG pattern is rare in the general Danish population. None of the subjects with a Brugada-type ECG died suddenly during a follow-up of 6-33 years. © The Author 2010.

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