Faculty Collaboration Database

Stage-dependent activation of cell cycle and apoptosis mechanisms in the right ventricle by pressure overload. Biochim Biophys Acta 2002 Apr 24;1586(3):233-42

Date

05/09/2002

Pubmed ID

11997075

DOI

10.1016/s0925-4439(01)00101-6

Scopus ID

2-s2.0-0037165696 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

The molecular basis of the intrinsic vulnerability of the compliant right ventricle to chronic pressure overload is poorly understood. Extensive apoptosis, possibly coupled with aberrant cell cycle reentry, in response to unrestrained biomechanical stress may account for this phenotypic flaw. To address this issue we have studied changes in expression of the cell cycle and apoptosis regulators in the right ventricle following induction of pulmonary hypertension in the rat by injection of monocrotaline. Hypertrophy, apoptosis and cell cycle events, as well as expression of their regulator genes were documented during a period of 31 days. The hypertrophy index reached 127% at day 31. At the early stage both apoptosis and cell proliferation pathways were coincidentally activated. The level of cyclin A and E transcripts steadily increased, the labeling index was 4.8% at day 31, and expression of the caspase-3 gene peaked at day 14. Until day 21 execution of apoptosis was prevented, probably by a high level of Bcl-2. At this time point Bcl-2 collapsed, cyclin D1 was upregulated, the differentiation gatekeeper p27Kip1 was downregulated, pro-caspase-3 was activated and extensive apoptosis developed. These results indicate that the right ventricle is especially vulnerable to apoptotic pressure-dependent stimuli, and that the cell cycle and apoptosis pathways were co-activated in this experimental model.

Author List

Ecarnot-Laubriet A, Assem M, Poirson-Bichat F, Moisant M, Bernard C, Lecour S, Solary E, Rochette L, Teyssier JR

Author

Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Apoptosis
Cell Cycle
Disease Models, Animal
Heart
Heart Ventricles
Hypertrophy, Left Ventricular
Immunohistochemistry
Myocardium
Pressure
RNA, Messenger
Rats
Receptor, Angiotensin, Type 1
Receptors, Angiotensin
Reverse Transcriptase Polymerase Chain Reaction