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The role of cyclin‐dependent kinase 6 in cardiac development and hypertrophy
Author(s) -
Bryan Crystal,
Blanton Robert,
Aronovitz Mark,
Karas Richard,
Hu Miaofen,
Hinds Philip W.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb35
Subject(s) - cyclin dependent kinase 6 , cyclin dependent kinase , heart failure , cardiac function curve , cyclin , muscle hypertrophy , medicine , cell cycle , kinase , endocrinology , biology , microbiology and biotechnology , cardiology , cancer
Heart failure affects 1–3% of people in the Western world and is strongly associated with cardiac hypertrophy. Studies have linked the cell cycle machinery to this process, but the role of cyclins and cyclin‐dependent kinases (cdks) remains poorly understood. Our research focuses on the role of the G1 cell cycle regulator cdk6 during normal development and cardiac stress. Cdk6 acts with D‐type cyclins to promote S‐phase entry in proliferating cells, but is also known to be induced concomitant with cardiac hypertrophy after transaortic constriction (TAC). Through in vivo studies utilizing cdk6 knockout (KO) mice, we observed decreased heart weight/tibia length ratios in KO mice. One objective of this project is to understand how cdk6 regulates cardiac size. Our data indicate that cdk6 is required for proper levels of proliferation and timing of differentiation of embryonic cardiomyocytes. Another objective of this project is to study the role of cdk6 in cardiac stress. Our ongoing studies suggest that cdk6 loss may impair harmful cardiac remodeling which leads to heart failure. We observe blunted hypertrophy in response to TAC in KO animals, with IL‐1β playing a key role. If this suppression of pathologic hypertrophy is accompanied by superior function following TAC, therapeutics targeting cdk6 may be indicated following cardiac injury to reduce the possibility of subsequent heart failure.