Myocardial Proinflammatory Cytokine Expression and Left Ventricular Remodeling in Patients With Chronic Mitral Regurgitation

Oral, Hakan; Sivasubramanian, Natarajan; Dyke, David B.; Mehta, Rajendra H.; Grossman, Paul; Briesmiester, Kerri; Fay, William P.; Pagani, Francis D.; Bolling, Steven F.; Mann, Douglas L.; Starling, Mark R.

doi:10.1161/01.cir.0000049745.38594.6d

Cited by 74 publications

(51 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the genes analyzed, TNF-α, IL-6, and TGF-β1 were found to be highly up-regulated by almost 3-to 5-fold in the mutant mice hearts. Myocardial cytokine genes such as TNF-α, IL-1β and IL-6 expression were found to be higher in patients with compensated heart failure condition, and it has been suggested that increased cytokine gene expression has adaptive role in the left ventricular remodeling process (22). Experimental induction of hemodynamic overload in the adult mammalian heart has been shown to provoke a transient increase in pro-inflammatory cytokines (2).…”

Section: Discussionmentioning

confidence: 99%

Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A

2007

View full text Add to dashboard Cite

Natriuretic peptide receptor-A (NPRA) is the principal receptor for the cardiac hormones ANP and BNP. Mice lacking NPRA develop progressive cardiac hypertrophy and congestive heart failure. However, the mechanisms responsible for hypertrophic growth in the absence of NPRA signaling are not yet known. In the present study, we determined whether deficiency of NPRA/cGMP signaling alters the cardiac pro-inflammatory cytokines gene expression in Npr1 (coding for NPRA) geneknockout (Npr1 −/− ) mice exhibiting cardiac hypertrophy and fibrosis as compared with control wildtype (Npr1 +/+ ) mice. A significant up-regulation of cytokine genes such as TNF-α (5-fold), IL-6 (3-fold) and TGF-β1 (4-fold) were observed in mutant mice hearts lacking NPRA as compared with the age-matched wild-type mice. In parallel, NF-κB binding activity was almost 5-fold greater in the nuclear extract of Npr1 −/− mutant mice hearts as compared with wild-type Npr1 +/+ mice hearts. Guanylyl cyclase (GC) activity and cGMP levels were drastically reduced by 10-fold and 6-fold, respectively, in ventricular tissues of mutant mice hearts relative to wild-type controls. The present findings provide direct evidence that ablation of NPRA/cGMP signaling activates inflammatory cytokines, probably via NF-κB mediated signaling pathway, and is associated with hypertrophic growth of null mutant mice hearts.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A

2007

View full text Add to dashboard Cite

show abstract

“…Proinflammatory cytokines are increased in the myocardium as a response to stretch in MR patients and correlate with the extent of LV dilatation. 37 Inflammatory response and cytokine elaboration are integral components of the host response to tissue injury and play an active role in myocardial remodeling, and thus inflammatory mediators play a crucial role in the development of heart failure. Accordingly, several strategies to counterbalance the inflammatory response have been suggested.…”

Section: Kim Et Al Effect Of Sildenafil On Mitral Regurgitation 1399mentioning

confidence: 99%

Long-Term Effects of Sildenafil in a Rat Model of Chronic Mitral Regurgitation

Kim

Ohn²,

Yang

et al. 2012

Circulation

View full text Add to dashboard Cite

Background— We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR). Methods and Results— MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P <0.05; LV end-diastolic dimension, 8.3±0.4 versus 10.5±0.2 versus 11.7±0.61 mm, respectively; P <0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2±2.2 for sham versus 67.0±4.2 for MR+sildenafil versus 58.9±2.5 for MR; P =0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling–positive cells was 2-fold greater in the MR compared with the MR+sildenafil group. Conclusions— Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil.

show abstract

“…Myocardial pressure overload and myocardial fiber distension provide sufficient stimulation to stimulate the secretion of TNF by the cardiac myocytes 5 , increasing their genic expression 5 and triggering a chain reaction that also increases the levels of other cytokines 6 . The natriuretic peptides, especially the B-type natriuretic peptide (BNP) are other examples of proteins of which secretion is stimulated by mechanical stress to the myocardium.…”

Section: Spina Et Al Neurohormonal Profile Of Aortic Regurgitationmentioning

confidence: 99%

Perfil neuro-hormonal de pacientes reumáticos com insuficiência aórtica crônica importante

Spina

Tarasoutchi

Sampaio

et al. 2009

Arq. Bras. Cardiol.

View full text Add to dashboard Cite

show abstract

Myocardial Proinflammatory Cytokine Expression and Left Ventricular Remodeling in Patients With Chronic Mitral Regurgitation

Cited by 74 publications

References 29 publications

Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A

Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A

Long-Term Effects of Sildenafil in a Rat Model of Chronic Mitral Regurgitation

Perfil neuro-hormonal de pacientes reumáticos com insuficiência aórtica crônica importante

Contact Info

Product

Resources

About