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Genetics of systolic and diastolic heart failure

Alan Y Deng1

  • 1Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.

Journal of Hypertension
|November 8, 2014
PubMed

Insights

Genetic studies reveal key genes and pathways involved in systolic and diastolic heart failure. Combining multiple genetic factors offers long-term protection against diastolic dysfunction, paving the way for new therapies.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Heart Failure Pathophysiology

Background:

  • Heart failure, encompassing systolic (SHF) and diastolic (DHF) types, significantly impacts cardiovascular health.
  • While human genome-wide association studies (GWAS) have identified markers for SHF, DHF lacks comprehensive GWAS.
  • Understanding the genetic underpinnings of left ventricular dysfunction is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the genetic components, specifically quantitative trait loci (QTLs), that regulate systolic and diastolic function in heart failure models.
  • To identify candidate genes associated with SHF and DHF.
  • To explore therapeutic strategies for ameliorating and reversing heart failure by targeting identified genetic factors.

Main Methods:

  • Genetic analyses in rat models of SHF and DHF.
  • Identification of quantitative trait loci (QTLs) influencing systolic and diastolic function.
  • Gene candidate identification, including soluble epoxide hydrolase for systolic function and Ccl2 for diastolic function.

Main Results:

  • A specific QTL for systolic function was linked to the gene encoding soluble epoxide hydrolase.
  • Multiple QTLs were implicated in diastolic function, with the Ccl2 gene being a strong candidate.
  • Transient improvement in diastolic dysfunction was observed with single QTL modification and blood pressure reduction, but long-term protection required combining multiple QTLs.

Conclusions:

  • Distinct genes act synergistically to durably ameliorate or reverse diastolic dysfunction.
  • These findings provide a foundation for identifying causal genes and their combinations for permanent protection against diastolic dysfunction.
  • Novel pathways identified offer potential for new diagnostic tools and therapeutic targets for both SHF and DHF, including hypertensive diastolic dysfunction.

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