Our results highlight the interaction of Yulink with PPARγ in regulating Serca2 expression and suggest a mechanistic role of the Yulink in the development of human heart failure and SCD.-Tsai, C.-T., Kuo, M.-W., Lin, J.-L., Yu, A. L., Yu, J.
Our findings show a crucial role of LRP1/Pyk2/HIF-1α in hypoxia-induced cardiomyocyte SERCA2 downregulation, a pathophysiological process closely associated with heart failure.
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.
In this review we describe the drugs adopted in clinical practice that activate SERCA2a/b function as well as new promising therapeutic tools using SERCA2 viral gene delivery to improve cardiac function and treat heart failure.
A reduced activity and expression of SERCA2 protein have been described in heart failure and diabetic cardiomyopathy, resulting in an altered Ca(2+) handling and cardiac contractility.
The observation that ATP2A2rs1860561 gene variant associated with lower risk of life-threatening arrhythmia in HF patients suggests that selected calcium gene variants may modify the risk of SD even within the complex and polygenic pathological condition of HF.
Therapeutic upregulation of SERCA2 expression using replication deficient adenoviral expression vectors, pharmacological interventions using thyroid hormone analogues, beta-adrenergic receptor antagonists, and novel metabolically active compounds are currently under investigation for the treatment of uncompensated cardiac hypertrophy and heart failure.
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.
Chronically elevated angiotensin II is a widely-established contributor to hypertension and heart failure via its action on the kidneys and vasculature.
Substantial evidence suggests that heart failure (HF) may alter cardiac Ang-(1-12) expression and activity; this novel Ang-(1-12)/chymase axis may be the main source for angiotensin-II deleterious actions in HF.
All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior.
Endothelin 1 Is Associated with Heart Failure Hospitalization and Long-Term Mortality in Patients with Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension.
Other cardiovascular complications seen in GBS patients were Increased pro-BNP(26.04%), raised troponin T levels(3.12%), acute coronary syndrome(2.08%), heart failure(2.08%) and abnormal 2D echo findings(8.33%).
Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling.
Therapy with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is a mainstay of treatment for heart failure (HF), diabetes mellitus (DM) and chronic kidney disease (CKD).
Inhibition of RAAS using angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) have shown to significantly reduce morbidity and mortality due to HF.
We illustrate the merits of our proposed approach with a detailed analysis of two large clinical trials (N = 6769) for the prevention and treatment of congestive heart failure using an angiotensin-converting enzyme inhibitor.