Analysis of animal models suggests that by activation of these homeostatic mechanisms, HIF-1 plays a critical protective role in the pathophysiology of ischemic heart disease and pressure-overload heart failure.
Last, we will update the readers on the current status of GRK2 inhibitors as a potential therapeutic strategy for heart failure with an emphasis on their ability of rescuing NO bioavailability.
It has been shown that lowering cardiac G-protein-coupled-receptor-kinase-2 (GRK2) activity with βARKct expression, a peptide inhibitor of protein-coupled-receptor-kinase-2 (GRK2), results in improvement of heart failure in several different animal models.
As angiotensin II regulates both glomerular filtration rate (GFR) and erythropoiesis, RAS inhibition can further deteriorate renal function and lower hematocrit or cause anaemia in patients with heart failure.
Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker responses in hypertension and heart failure.
The target of the current study was to examine the possible cardioprotective effect of telmisartan (Tel), an angiotensin II type 1 receptor (AT1R) blocker, compared with that of captopril (Cap), an angiotensin converting enzyme (ACE) inhibitor, in ameliorating PRG-induced HF in rats by assessing morphometric, echocardiographic and histopathological parameters.
The standard pharmacotherapy for heart failure (HF), particularly HF with reduced ejection fraction (HFrEF), is primarily through the use of receptor antagonists, notably inhibition of the renin-angiotensin system by either angiotensin-converting enzyme inhibition or angiotensin II receptor blockade (ARB).
The target of the current study was to examine the possible cardioprotective effect of telmisartan (Tel), an angiotensin II type 1 receptor (AT1R) blocker, compared with that of captopril (Cap), an angiotensin converting enzyme (ACE) inhibitor, in ameliorating PRG-induced HF in rats by assessing morphometric, echocardiographic and histopathological parameters.
Several polymorphisms that have supporting molecular and clinical data in the heart failure literature are reviewed, among them the beta1-adrenergic receptor variant Arg389Gly and the angiotensin converting enzyme gene insertion/deletion polymorphism.
These data reveal myofibrillar Ca(2+)-sensitivity to be an important determinant of the cardiac effects of SERCA2 haploinsufficiency and raise the possibility that Darier disease patients are more susceptible to heart failure under certain conditions.
Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for management of heart failure via genetic manipulation of beta-AR signaling including the targeted inhibition of the beta-AR kinase (betaARK1 or GRK2).
Although the first-in-class ARNi sacubitril/valsartan (LCZ696) reduced mortality and morbidity in heart failure (HF) with reduced ejection fraction (EF) compared to angiotensin converting enzyme inhibitor (ACEi), mechanistic data on ARNi are scarce.
The advanced heart failure and transplant programme formulated an institutional protocol for initiation of sacubitril/valsartan with defined criteria for switching from angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB).
Using the 2008-2012 IBM MarketScan Commercial database, we followed 26,439 individuals aged 18-64 years with newly diagnosed HF and calculated their adherence (using the proportion of days covered (PDC) algorithm) to the five guideline-recommended medication categories: angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers; beta blockers; aldosterone receptor antagonists; hydralazine; and isosorbide dinitrate.
Multivariate analysis revealed that several variables (including gender, hypertension, renal dysfunction, TIMI flow grade post-PCI < 3, and treatment administered after PCI with betablockers and angiotensin-converting enzyme inhibitors) had per se a significant influence on the occurrence of [death or hospitalization for heart failure] at 1 year.
At discharge, women less frequently received ACE inhibitors (189 [81.1%] vs. 702 [85.8%], p=0.045) and presented more major adverse events (death, bleeding, infection, myocardial infarction, stent thrombosis or heart failure) during the first month after discharge (10.5% vs. 4.5%, p<0.001) and higher long-term mortality (hazard ratio [HR] 1.6, 95% CI 1.1-2.2).
Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment.
For example, GWAS of NT-proBNP levels not only identified variants in the NNPA-NPPB locus but also substantiated data suggesting that natriuretic peptides in itself are associated with a lower risk of hypertension and HF.
There is currently no consensus on the effect of treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), on the prognosis of patients with heart failure and preserved ejection fraction (HFpEF).
Increasing the expression of GTP cyclohydrolase 1, the rate-limiting enzyme in the de novo biosynthesis of tetrahydrobiopterin, exercise training couples endothelial nitric oxide synthase, reduces oxidative stress, and increases nitric oxide bioavailability and sensitivity in coronary arteries of heart failure rats.
During end-stage human heart failure, we have demonstrated that type 1 IP3R (IP3R1) mRNA and protein levels are up-regulated, in contrast to other cardiac calcium regulatory proteins, such as the type 2 ryanodine receptor (RYR2) and type IIa sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2), which are down-regulated.
Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) were administered in 68.9% of HF discharged patients, beta-blockers in 84.8%, mineralocorticoid receptor antagonist (MRA) in 57.9%, diuretics in 85.9%, and digoxin in 23%.
A polymorphism within tumor necrosis factor-α (TNF-α) gene promoter and contribution of TNF-α converting enzyme (TACE) have been reported to be associated with TNF-α production which may increase susceptibility to heart failure such as acute myocardial infarction (AMI).