Cardiovascular Institute of the South

About: Cardiovascular Institute of the South is a other organization based out in Houma, Louisiana, United States. It is known for research contribution in the topics: Myocardial infarction & Population. The organization has 6744 authors who have published 6131 publications receiving 175736 citations.

Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo.

Abstract: Recent work from this laboratory demonstrated that apoptosis of pulmonary alveolar epithelial cells (AEC) in response to Fas requires angiotensin II (ANGII) generation de novo and binding to its receptor (Wang et al., 1999b, Am J Physiol Lung Cell Mol Physiol 277:L1245-L1250). These findings led us to hypothesize that a similar mechanism might be involved in the induction of AEC apoptosis by TNF-alpha. Apoptosis was detected by assessment of nuclear and chromatin morphology, increased activity of caspase 3, binding of annexin V, and by net cell loss inhibitable by the caspase inhibitor ZVAD-fmk. Purified human TNF-alpha induced dose-dependent apoptosis in primary type II pneumocytes isolated from rats or in the AEC-derived human lung carcinoma cell line A549. Apoptosis in response to TNF-alpha was inhibited in a dose-dependent manner by the nonselective ANGII receptor antagonist saralasin or by the nonthiol ACE inhibitor lisinopril; the inhibition of TNF-induced apoptosis was maximal at 50 microgram/ml saralasin (101% inhibition) and at 0.5 microgram/ml lisinopril (86% inhibition). In both cell culture models, purified TNF-alpha caused a significant increase in the mRNA for angiotensinogen (ANGEN), which was not expressed in unactivated cells. Transfection of primary cultures of rat AEC with antisense oligonucleotides against ANGEN mRNA inhibited the subsequent induction of TNF-stimulated apoptosis by 72% (P < 0.01). Exposure to TNF-alpha increased the concentration of ANGII in the serum-free extracellular medium by fivefold in A549 cell cultures and by 40-fold in primary AEC preparations; further, exposure to TNF-alpha for 40 h caused a net cell loss of 70%, which was completely abrogated by either the caspase inhibitor ZVAD-fmk, lisinopril, or saralasin. Apoptosis in response to TNF-alpha was also completely inhibited by neutralizing antibodies specific for ANGII (P < 0.01), but isotype-matched nonimmune immunoglobulins had no significant effect. These data indicate that the induction of AEC apoptosis by TNF-alpha requires a functional renin/angiotensin system (RAS) in the target cell. They also suggest that therapeutic control of AEC apoptosis in response to TNF-alpha is feasible through pharmacologic manipulation of the local RAS.

Reactive and reparative fibrillar collagen remodelling in the hypertrophied rat left ventricle: two experimental models of myocardial fibrosis

Abstract: Study objective – The aim was to compare the temporal sequence and structural relationship between perivascular and interstitial fibrosis and microscopic scarring seen in the left ventricle in response to either a transient or sustained stimulus to fibrosis. Design – In 72 male Wistar rats (250 – 350 g) the transient stimulus model was based on the administration of isoprenaline (500 μg·kg−1) while the sustained stimulus model was produced by abdominal aortic banding with right renal artery constriction. Serial sections of myocardium were examined and compared at 4 and 12 weeks in each model and to corresponding controls. Experimental material – The collagen specific stain, Sirius Red F3BA, was used to determine collagen volume fraction and the fibrillar nature of the fibrous tissue response seen by light microscopy. Measurements and main results – Following isoprenaline a stable reparative fibrosis of the endomyocardium and increase in collagen volume fraction was seen without an interstitial or perivascular fibrosis of the non-involved myocardium. In unilateral renal ischaemia, on the other hand, a progressive perivascular fibrosis was evident throughout the myocardium and from which fibrillar collagen extended into the extracellular space between muscle bundles creating an interstitial fibrosis; microscopic scarring of the endomyocardium became evident at 12 weeks. Conclusions – The reactive perivascular fibrosis of intramyocardial coronary arteries seen in renovascular hypertension is a progressive process that leads to an interstitial fibrosis and eventual microscopic scarring. In contrast, the endomyocardial scarring that follows isoprenaline induced myocyte necrosis is stable and intramural vessels in remote regions are not involved.

Calcium-dependent arrhythmias in transgenic mice with heart failure.

Abstract: Transgenic mice overexpressing the inflammatory cytokine tumor necrosis factor (TNF)-α (TNF-α mice) in the heart develop a progressive heart failure syndrome characterized by biventricular dilatati...

Association Between Intensity of Statin Therapy and Mortality in Patients With Atherosclerotic Cardiovascular Disease.

Abstract: Importance High-intensity statin therapy is recommended for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Nevertheless, statin therapy in general, and high-intensity statin therapy in particular, is underused in patients with established ASCVD. Objective To determine the association between all-cause mortality and intensity of statin therapy in the Veterans Affairs health care system. Design, Setting, and Participants A retrospective cohort analysis was conducted of patients aged 21 to 84 years with ASCVD treated in the Veterans Affairs health care system from April 1, 2013, to April 1, 2014. Patients who were included had 1 or more International Classification of Diseases, Ninth Revision codes for ASCVD on 2 or more different dates in the prior 2 years. Exposures Intensity of statin therapy was defined by the 2013 American College of Cardiology/American Heart Association guidelines, and use was defined as a filled prescription in the prior 6 months. Patients were excluded if they were taking a higher statin dose in the prior 5 years. Main Outcomes and Measures The primary outcome was death from all causes adjusted for the propensity to receive high-intensity statins. Results The study sample included 509 766 eligible adults with ASCVD at baseline (mean [SD] age, 68.5 [8.8] years; 499 598 men and 10 168 women), including 150 928 (29.6%) receiving high-intensity statin therapy, 232 293 (45.6%) receiving moderate-intensity statin therapy, 33 920 (6.7%) receiving low-intensity statin therapy, and 92 625 (18.2%) receiving no statins. During a mean follow-up of 492 days, there was a graded association between intensity of statin therapy and mortality, with 1-year mortality rates of 4.0% (5103 of 126 139) for those receiving high-intensity statin therapy, 4.8% (9703 of 200 709) for those receiving moderate-intensity statin therapy, 5.7% (1632 of 28 765) for those receiving low-intensity statin therapy, and 6.6% (4868 of 73 728) for those receiving no statin ( P Conclusions and Relevance We found a graded association between intensity of statin therapy and mortality in a national sample of patients with ASCVD. High-intensity statins were associated with a small but significant survival advantage compared with moderate-intensity statins, even among older adults. Maximal doses of high-intensity statins were associated with a further survival benefit.