Profilin-1 promotes the development of hypertension-induced cardiac hypertrophy.

Abstract

OBJECTIVE:

Cardiac hypertrophy is a major cause of heart failure and sudden cardiac death among hypertensive individuals. The present study examined the effects of profilin-1 on hypertension-induced cardiac hypertrophy.

METHODS:

We used adenovirus injection to knockdown or overexpress profilin-1 in spontaneous hypertensive rats (SHRs). As a control, blank adenovirus was injected into age-matched SHRs and Wistar-Kyoto rats (WKYs). SBP and cardiac mass index were measured. Cardiac tissues were stained with hematoxylin-eosin and sirius red, and cardiac ultrastructure was imaged using transmission electron microscopy. Actin filament was quantified by staining with TRIC-tagged phalloidin. Caveolin-3 abundance and endothelial nitric oxide synthase (eNOS) activity were measured using real-time quantitative PCR, Western blot or immunofluorescence staining.

RESULTS:

Endogenous profilin-1 was highly expressed in hypertrophic myocardium of SHRs compared with WKYs. Lowering profilin-1 expression in SHRs significantly attenuated hypertension-induced cardiac hypertrophy and fibrosis and displayed a significant preservation of myofibrils, sarcolemmal caveolae, abundance of caveolin-3 protein, activity of eNOS and production of nitric oxide (NO). In contrast, transgenic overexpression of profilin-1 in SHRs induced more serious cardiac hypertrophy and fibrosis with significant reduction of sarcolemmal caveolae, caveolin-3 protein, eNOS activity, and production of NO when compared with SHR controls.

CONCLUSION:

Profilin-1 promotes cardiac hypertrophy partly through interfering with the formation of sarcolemmal caveolae and attenuating the eNOS/NO pathway. These results demonstrate a crucial role for profilin-1 in hypertensive cardiac hypertrophy.

• Authors: Shao-hua Zhao, Jie Qiu, Yan Wang, Xiang Ji, Xiang-ju Liu, Bei-an You, Yu-ping Sheng, Xiao Li, Hai-qing Gao
• Journal: Journal of hypertension (J Hypertens) Vol. 31 Issue 3 Pg. 576-86; discussion 586 (Mar 2013) ISSN: 1473-5598 [Electronic] England
• PMID: 23615214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Pfn1 protein, rat
• Profilins

Topics

• Animals
• Base Sequence
• Cardiomegaly (physiopathology)
• DNA Primers
• Hypertension (physiopathology)
• Male
• Profilins (physiology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Real-Time Polymerase Chain Reaction