Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

O Lynne Nelson; Charles T Robbins; Yiming Wu; Henk Granzier

doi:10.1152/ajpheart.00234.2008

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Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

Journal article

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Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

O Lynne Nelson, Charles T Robbins, Yiming Wu and Henk Granzier

American journal of physiology. Heart and circulatory physiology, Vol.295(1), pp.H366-371

07/2008

DOI: https://doi.org/10.1152/ajpheart.00234.2008

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https://hdl.handle.net/2376/107745

PMCID: PMC2494771

PMID: 18502907

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Abstract

Protein Kinases - metabolism

Heart Rate

Protein Kinases - genetics

Collagen Type I - metabolism

Connectin

Alternative Splicing

Compliance

Ventricular Function, Left

Isoenzymes

Cardiac Output

Collagen Type III - metabolism

Bradycardia - physiopathology

Bradycardia - diagnostic imaging

Muscle Proteins - genetics

Myocardium - enzymology

Ventricular Remodeling

Animals

Ursidae - metabolism

Heart Ventricles - enzymology

Hibernation

Muscle Proteins - metabolism

Ultrasonography

Bradycardia - enzymology

Female

The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly bears.

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Title: Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears
Creators: O Lynne Nelson - College of Veterinary Medicine, Washington State Univ., Pullman, WA 99164, USA. olnelson@vetmed.wsu.edu
Charles T Robbins
Yiming Wu
Henk Granzier
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.295(1), pp.H366-371
Academic Unit: Integrative Physiology and Neuroscience, Department of; Environment, School of the (CAHNRS)
Publisher: United States
Grant note: HL-062881 / NHLBI NIH HHS
Identifiers: 99900547238601842
Language: English
Resource Type: Journal article