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Nuclear factor-kappaB signaling contributes to severe, but not moderate, angiotensin II-induced left ventricular remodeling.
J Hypertens. 2007 Sep; 25(9):1927-39.JH

Abstract

OBJECTIVE

The transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated in cardiomyocyte hypertrophy in vitro as well as in vivo; however, it is unknown if activation of NF-kappaB plays a mandatory role in the hypertrophic process. Here we characterize the importance of NF-kappaB signaling in moderate and severe left ventricular (LV) hypertrophy in rats with chronic pressure overload induced by angiotensin II (Ang II) infusion.

METHODS AND RESULTS

Electrophoretic mobility shift assay analysis revealed that Ang II infusion (2.5 microg/kg per min) for 6 days increased LV NF-kappaB/DNA-binding activity in a biphasic manner in Sprague-Dawley rats. Pyrrolidine dithiocarbamate (PDTC) (100 mg/kg per day), an NF-kappaB inhibitor, abolished Ang II-induced NF-kappaB activation and concomitant increase in tumor necrosis factor-alpha gene expression, while activator protein-1/DNA binding was not affected. Inhibition of NF-kappaB signaling for 6 days significantly attenuated Ang II-induced increases in LV/body weight ratio, LV mean wall thickness and cardiomyocyte cross-sectional area, without compromising LV systolic function. Moreover, PDTC abolished Ang II-induced cardiomyocyte apoptosis and interstitial fibrosis, and attenuated the gene expression of type I collagen. In contrast, a moderate LV hypertrophy induced by Ang II at a lower dose (0.5 microg/kg per min) was not associated with a significant activation of NF-kappaB, and PDTC treatment had no effect on the hypertrophic indices.

CONCLUSION

Our in-vivo data indicate a critical role of NF-kappaB signaling in the advanced stage of the remodeling process, whereas development of moderate LV hypertrophy is not dependent on NF-kappaB activation.

Authors+Show Affiliations

First Department of Medicine, Semmelweis University, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

17762659

Citation

Sármán, Balázs, et al. "Nuclear factor-kappaB Signaling Contributes to Severe, but Not Moderate, Angiotensin II-induced Left Ventricular Remodeling." Journal of Hypertension, vol. 25, no. 9, 2007, pp. 1927-39.
Sármán B, Skoumal R, Leskinen H, et al. Nuclear factor-kappaB signaling contributes to severe, but not moderate, angiotensin II-induced left ventricular remodeling. J Hypertens. 2007;25(9):1927-39.
Sármán, B., Skoumal, R., Leskinen, H., Rysä, J., Ilves, M., Soini, Y., Tuukkanen, J., Pikkarainen, S., Lakó-Futó, Z., Sármán, B., Papp, L., deChâtel, R., Tóth, M., Ruskoaho, H., & Szokodi, I. (2007). Nuclear factor-kappaB signaling contributes to severe, but not moderate, angiotensin II-induced left ventricular remodeling. Journal of Hypertension, 25(9), 1927-39.
Sármán B, et al. Nuclear factor-kappaB Signaling Contributes to Severe, but Not Moderate, Angiotensin II-induced Left Ventricular Remodeling. J Hypertens. 2007;25(9):1927-39. PubMed PMID: 17762659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear factor-kappaB signaling contributes to severe, but not moderate, angiotensin II-induced left ventricular remodeling. AU - Sármán,Balázs, AU - Skoumal,Réka, AU - Leskinen,Hanna, AU - Rysä,Jaana, AU - Ilves,Mika, AU - Soini,Ylermi, AU - Tuukkanen,Juha, AU - Pikkarainen,Sampsa, AU - Lakó-Futó,Zoltán, AU - Sármán,Beatrix, AU - Papp,Lajos, AU - deChâtel,Rudolf, AU - Tóth,Miklós, AU - Ruskoaho,Heikki, AU - Szokodi,István, PY - 2007/9/1/pubmed PY - 2007/10/25/medline PY - 2007/9/1/entrez SP - 1927 EP - 39 JF - Journal of hypertension JO - J Hypertens VL - 25 IS - 9 N2 - OBJECTIVE: The transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated in cardiomyocyte hypertrophy in vitro as well as in vivo; however, it is unknown if activation of NF-kappaB plays a mandatory role in the hypertrophic process. Here we characterize the importance of NF-kappaB signaling in moderate and severe left ventricular (LV) hypertrophy in rats with chronic pressure overload induced by angiotensin II (Ang II) infusion. METHODS AND RESULTS: Electrophoretic mobility shift assay analysis revealed that Ang II infusion (2.5 microg/kg per min) for 6 days increased LV NF-kappaB/DNA-binding activity in a biphasic manner in Sprague-Dawley rats. Pyrrolidine dithiocarbamate (PDTC) (100 mg/kg per day), an NF-kappaB inhibitor, abolished Ang II-induced NF-kappaB activation and concomitant increase in tumor necrosis factor-alpha gene expression, while activator protein-1/DNA binding was not affected. Inhibition of NF-kappaB signaling for 6 days significantly attenuated Ang II-induced increases in LV/body weight ratio, LV mean wall thickness and cardiomyocyte cross-sectional area, without compromising LV systolic function. Moreover, PDTC abolished Ang II-induced cardiomyocyte apoptosis and interstitial fibrosis, and attenuated the gene expression of type I collagen. In contrast, a moderate LV hypertrophy induced by Ang II at a lower dose (0.5 microg/kg per min) was not associated with a significant activation of NF-kappaB, and PDTC treatment had no effect on the hypertrophic indices. CONCLUSION: Our in-vivo data indicate a critical role of NF-kappaB signaling in the advanced stage of the remodeling process, whereas development of moderate LV hypertrophy is not dependent on NF-kappaB activation. SN - 0263-6352 UR - https://www.unboundmedicine.com/medline/citation/17762659/Nuclear_factor_kappaB_signaling_contributes_to_severe_but_not_moderate_angiotensin_II_induced_left_ventricular_remodeling_ L2 - https://doi.org/10.1097/HJH.0b013e3281e66653 DB - PRIME DP - Unbound Medicine ER -