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Vinculin-network mediated cytoskeletal remodeling regulates contractile function in the aging heart - Rat Data

ABSTRACT: The human heart is capable of functioning for decades despite minimal cell turnover or regeneration, suggesting that molecular alterations help sustain heart function with age. However, identification of compensatory remodeling events in the aging heart remains elusive. Here we present the proteomes of rhesus monkeys and rats, from which we show that age-associated remodeling of the cardiomyocyte cytoskeleton is highly-conserved and beneficial rather than deleterious. Targeted transcriptomic analysis in Drosophila confirms conservation and implicates vinculin as a unique regulator of cardiac aging. Increased cardiac vinculin expression reinforced the cortical cytoskeleton and enhanced myofilament organization, leading to improved contractility, hemodynamic stress tolerance, and lifespan. These findings suggest that the heart has molecular mechanisms to sustain function and longevity which may be assisted by therapeutic intervention.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Vidya Venkatraman

LAB HEAD: Dr. Jennifer Van Eyk

PROVIDER: PXD001839 | Pride | 2016-04-15

REPOSITORIES: Pride

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Vinculin network-mediated cytoskeletal remodeling regulates contractile function in the aging heart.

Kaushik Gaurav G Spenlehauer Alice A Sessions Ayla O AO Trujillo Adriana S AS Fuhrmann Alexander A Fu Zongming Z Venkatraman Vidya V Pohl Danielle D Tuler Jeremy J Wang Mingyi M Lakatta Edward G EG Ocorr Karen K Bodmer Rolf R Bernstein Sanford I SI Van Eyk Jennifer E JE Cammarato Anthony A Engler Adam J AJ

Science translational medicine 20150601 292

The human heart is capable of functioning for decades despite minimal cell turnover or regeneration, suggesting that molecular alterations help sustain heart function with age. However, identification of compensatory remodeling events in the aging heart remains elusive. We present the cardiac proteomes of young and old rhesus monkeys and rats, from which we show that certain age-associated remodeling events within the cardiomyocyte cytoskeleton are highly conserved and beneficial rather than del ...[more]

PMID: 26084806

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