Unique quantitative trait loci in synergy permanently improve diastolic dysfunction
| Autor: | Stanley Nattel, Nathalie L'Heureux, Danielle Gelinas, Yanfen Shi, Jean-Claude Tardif, Cristina Chauvet, Francine Duval, Alan Y. Deng, Kimberley Crespo |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Quantitative Trait Loci Congenic Diastole Blood Pressure Quantitative trait locus Left ventricular hypertrophy Ventricular Function Left Muscle hypertrophy Ventricular Dysfunction Left Animals Congenic Internal medicine medicine Animals cardiovascular diseases Rats Inbred Dahl business.industry Diastolic heart failure Chromosome Mapping Genetic Therapy medicine.disease Phenotype Rats Disease Models Animal Endocrinology Blood pressure Echocardiography Hypertrophy Left Ventricular Cardiology and Cardiovascular Medicine business |
| Zdroj: | The Canadian journal of cardiology. 29(10) |
| ISSN: | 1916-7075 |
| Popis: | Background Diastolic dysfunction often precedes the onset of diastolic heart failure. We previously demonstrated that diastolic dysfunction and left ventricular hypertrophy (LVH) in Dahl salt-sensitive rats can be ameliorated by quantitative trait loci (QTLs). Methods We analyzed cardiac phenotypes of 2 "single" congenic strains, C10S.L33 and C10S.L28, by echocardiography, in which a specific Dahl salt-sensitive rat chromosome segment was replaced by its Lewis homologue. C10S.L33 improves diastolic function (DF) and LVH only in rats aged 10 weeks, not aged 15 weeks. C10S.L28 alleviated LVH, but not diastolic dysfunction. Thus, the QTLs captured by C10S.L33 and C10S.L28 are designated as DF/LVH C10QTL7 and LVH C10QTL4 , respectively. We then combined multiple single strains to form 2 congenic combinations. One of the 2 congenic combinations included the chromosome segments covered by C10S.L33 and C10S.L28. Results Diastolic dysfunction was either completely or partially reversed by 15 weeks in the 2 congenic combinations. LVH was permanently improved from 10 to 15 weeks. Conclusions Distinct QTLs exist that regulate diastolic function and/or LVH in the short term when acting alone, but durably when combined. The Ccl2 chemokine (C-C motif) ligand 1 (Ccl2) gene is the prime candidate for DF/LVH C10QTL7 , owing to a nonconserved coding mutation. Schlafen genes are candidates for LVH C10QTL4 . Since CCL2 and Schlafens are not known for influencing diastolic function and left ventricular mass, novel long-term strategies of prognosis, diagnosis, and therapy for diastolic heart failure and LVH appear from this work. |
| Databáze: | OpenAIRE |
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