Tags

Type your tag names separated by a space and hit enter

Adverse biventricular remodeling in isolated right ventricular hypertension is mediated by increased transforming growth factor-β1 signaling and is abrogated by angiotensin receptor blockade.
Am J Respir Cell Mol Biol. 2013 Dec; 49(6):1019-28.AJ

Abstract

The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular-ventricular interactions lead to LV myocardial fibrosis through transforming growth factor-β1 (TGF-β1) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-β1, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2/3/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular-ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-β1-CTGF and ET-1 pathways.

Authors+Show Affiliations

1 Division of Cardiology, and.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23841477

Citation

Friedberg, Mark K., et al. "Adverse Biventricular Remodeling in Isolated Right Ventricular Hypertension Is Mediated By Increased Transforming Growth Factor-β1 Signaling and Is Abrogated By Angiotensin Receptor Blockade." American Journal of Respiratory Cell and Molecular Biology, vol. 49, no. 6, 2013, pp. 1019-28.
Friedberg MK, Cho MY, Li J, et al. Adverse biventricular remodeling in isolated right ventricular hypertension is mediated by increased transforming growth factor-β1 signaling and is abrogated by angiotensin receptor blockade. Am J Respir Cell Mol Biol. 2013;49(6):1019-28.
Friedberg, M. K., Cho, M. Y., Li, J., Assad, R. S., Sun, M., Rohailla, S., Honjo, O., Apitz, C., & Redington, A. N. (2013). Adverse biventricular remodeling in isolated right ventricular hypertension is mediated by increased transforming growth factor-β1 signaling and is abrogated by angiotensin receptor blockade. American Journal of Respiratory Cell and Molecular Biology, 49(6), 1019-28. https://doi.org/10.1165/rcmb.2013-0149OC
Friedberg MK, et al. Adverse Biventricular Remodeling in Isolated Right Ventricular Hypertension Is Mediated By Increased Transforming Growth Factor-β1 Signaling and Is Abrogated By Angiotensin Receptor Blockade. Am J Respir Cell Mol Biol. 2013;49(6):1019-28. PubMed PMID: 23841477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adverse biventricular remodeling in isolated right ventricular hypertension is mediated by increased transforming growth factor-β1 signaling and is abrogated by angiotensin receptor blockade. AU - Friedberg,Mark K, AU - Cho,Mi-Young, AU - Li,Jing, AU - Assad,Renato S, AU - Sun,Mei, AU - Rohailla,Sagar, AU - Honjo,Osami, AU - Apitz,Christian, AU - Redington,Andrew N, PY - 2013/7/12/entrez PY - 2013/7/12/pubmed PY - 2014/1/28/medline SP - 1019 EP - 28 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 49 IS - 6 N2 - The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular-ventricular interactions lead to LV myocardial fibrosis through transforming growth factor-β1 (TGF-β1) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-β1, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2/3/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular-ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-β1-CTGF and ET-1 pathways. SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/23841477/Adverse_biventricular_remodeling_in_isolated_right_ventricular_hypertension_is_mediated_by_increased_transforming_growth_factor_β1_signaling_and_is_abrogated_by_angiotensin_receptor_blockade_ L2 - http://www.atsjournals.org/doi/full/10.1165/rcmb.2013-0149OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -