Published Online
on February 9, 2009

A more recent version of this article appeared on March 1, 2009

This Article Full Text (PDF) Data Supplement All Versions of this Article: 53/3/539    most recent HYPERTENSIONAHA.108.120816v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cai, J. Articles by Yang, X.-C. Search for Related Content PubMed PubMed Citation Articles by Cai, J. Articles by Yang, X.-C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Related Collections Cardio-renal physiology/pathophysiology Remodeling Gene expression Hypertension - basic studies Hypertrophy Physiological and pathological control of gene expression Related Article

Submitted on July 31, 2008
Revised on August 24, 2008

Targeted Expression of Receptor-Associated Late Transducer Inhibits Maladaptive Hypertrophy via Blocking Epidermal Growth Factor Receptor Signaling

Jun Cai; Fang-Fang Yi; Long Yang; Di-Fei Shen; Qinling Yang; Ankang Li; Asish K. Ghosh; Zhou-Yan Bian; Ling Yan; Qi-Zhu Tang; Hongliang Li^*; and Xin-Chun Yang^*

From the Cardiovascular Research Center (J.C.), Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass; Department of Cardiology (J.C., F.F.Y., L.Yang, X.-C.Y.), Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Cardiovascular Research Institute of Wuhan University (D.-F.S., Z.-Y.B., L.Yan, Q.-Z.T., H.L.), Wuhan, China; Department of Cardiology (D.-F.S., Z.-Y.B., L.Yan, Q.-Z.T., H.L.), Renmin Hospital of Wuhan University, Wuhan, China; Department of Nutrition Sciences (Q.Y.), University of Alabama at Birmingham; Gene Expression Laboratory (A.L.), The Salk Institute for Biological Studies, La Jolla, Calif; and Division of Rheumatology (A.K.G.), Northwestern University Feinberg School of Medicine, Chicago, Ill.

^* To whom correspondence should be addressed. E-mail: lihl{at}whu.edu.cn or yangxc{at}medmail.com.cn.

Abstract—Receptor-associated late transducer (RALT) is a feedback inhibitor of epidermal growth factor receptor signaling. RALT has been shown previously to be induced in the ischemic heart and to promote cardiomyocyte apoptosis in vitro. However, the role of RALT in cardiac hypertrophy remains unclear. We hypothesized that forced expression of RALT in the murine heart would protect the heart against cardiac hypertrophy in vivo. We investigated the effect of cardiac overexpression of rat RALT on cardiac hypertrophy induced by angiotensin II and isoproterenol in RALT transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was assessed by 2D and M-mode echocardiography as well as by molecular and pathological analyses of cardiac samples. Constitutive expression of rat RALT in cardiac myocytes of murine heart attenuated both hypertrophic and inflammatory responses and preserved cardiac function. These beneficial effects were associated with the attenuation of the epidermal growth factor receptor–dependent cascade that was triggered by angiotensin II and isoproterenol stimulation. Additional evidence demonstrated that RALT expression blocked fibrosis in vivo and collagen synthesis in vitro. Therefore, cardiac overexpression of RALT improves cardiac function and inhibits maladaptive hypertrophy, inflammation, and fibrosis through attenuating epidermal growth factor receptor–dependent signaling.

Key words: RALT • EGFR • ERK1/2 • cardiac hypertrophy • heart failure • fibrosis

Related Article:

RALT Specifically Halts Maladaptive Cardiac Hypertrophy: A New Kid on the Block

Martin W. Bergmann and Laura Zelarayan
Hypertension 2009 53: 454-455. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				M. W. Bergmann and L. Zelarayan RALT Specifically Halts Maladaptive Cardiac Hypertrophy: A New Kid on the Block Hypertension, March 1, 2009; 53(3): 454 - 455. [Full Text] [PDF]