Unique quantitative trait loci in synergy permanently improve diastolic dysfunction.
Cristina Chauvet1, Kimberley Crespo, Yanfen Shi
1Research Centre, Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
The Canadian Journal of Cardiology
|June 19, 2013
Summary
Combining specific genetic regions (QTLs) durably improved diastolic function and left ventricular hypertrophy in rats. This suggests novel therapeutic targets for heart failure.
Area of Science:
- Cardiovascular Genetics
- Heart Failure Pathophysiology
- Animal Models of Hypertension
Background:
- Diastolic dysfunction often precedes diastolic heart failure.
- Quantitative trait loci (QTLs) have shown potential in ameliorating diastolic dysfunction and left ventricular hypertrophy (LVH).
Purpose of the Study:
- To investigate the long-term effects of combined QTLs on diastolic function (DF) and LVH.
- To identify specific QTLs responsible for DF and LVH in Dahl salt-sensitive rats.
Main Methods:
- Analysis of cardiac phenotypes in congenic rat strains (C10S.L33 and C10S.L28) using echocardiography.
- Creation of congenic combinations by merging chromosome segments from single strains.
- Assessment of diastolic function and LVH at 10 and 15 weeks of age.
Main Results:
- Single QTLs (DF/LVH C10QTL7 and LVH C10QTL4) showed short-term effects on DF and LVH.
- Combined QTLs demonstrated complete or partial reversal of diastolic dysfunction by 15 weeks.
- Left ventricular hypertrophy was permanently improved from 10 to 15 weeks in combined QTLs.
Conclusions:
- Distinct QTLs regulate short-term DF and LVH individually, but exhibit durable effects when combined.
- The Ccl2 gene is a prime candidate for DF/LVH C10QTL7, and Schlafen genes for LVH C10QTL4.
- Novel long-term strategies for diastolic heart failure and LVH prognosis, diagnosis, and therapy may emerge from these findings.
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