Heart failure explains a large portion of heart diseases. Molecular mechanisms determining cardiac function, by inference dysfunction in heart failure, are incompletely understood, especially in the common (or congestive) systolic (SHF) and diastolic heart failure (DHF). Limited genome-wide association studies (GWASs) in humans are reported on SHF and no GWAS has been performed on DHF. Genetic analyses in a rodent model of true DHF, Dahl salt-sensitive (DSS) rats, have begun to unravel the genetic components determining diastolic function. Diastolic dysfunction of DSS rats can be ameliorated or even normalized by distinct quantitative trait loci (QTLs), designated as diastolic function/blood pressure QTLs (DF/BP QTLs), which also affect blood pressure (BP). However, an improvement in diastolic dysfunction is merely transitory from a single DF/BP QTL, despite a permanent lowering of BP. A long-term protection against diastolic dysfunction can be realized only through combining specific DF/BP QTLs. Moreover, the worsening diastolic dysfunction with age can also be reversed in a different combination of DF/BP QTLs. Thus, distinct genes in combinations must be involved in the physiological mechanisms ameliorating or reversing diastolic dysfunction. As not all the QTLs that influence BP can affect diastolic function, it is not BP reduction itself that restores diastolic function, but rather specific genes that are uniquely integrated into the pathways of blood pressure homeostasis as well as diastolic function. Thus, the elucidation of pathophysiological mechanisms causal to hypertensive diastolic dysfunction will not only provide new diagnostic tools, but also novel therapeutic targets and strategies in reducing, curing, and even reversing DHF.
Research Centre, Centre hospitalier de l’Université de Montréal, Université de Montréal, Montréal, Québec, Canada
Correspondence to Alan Y. Deng, Research Centre, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, QC H1W 4A4, Canada. Tel: +1 514 890 8000x23614; fax: +1 514 412 7655; e-mail: email@example.com
Abbreviations: BP, blood pressure; CHF, common heart failure; Chr, chromosome; DHF, diastolic heart failure; DSS, Dahl salt-sensitive; GWAS, genome-wide association study; IVRT, isovolumetric relaxation time; MAP, mean arterial pressure; QTL, quantitative trait locus; SHF, systolic heart failure; SHHF, spontaneously hypertensive heart failure
Received 8 May, 2013
Revised 25 June, 2013
Accepted 25 July, 2013