The Year in Heart Failure

“…A lthough the clinical management of heart failure has advanced substantially, 1 and prevention strategies for atherosclerosis focused on managing the established risk factors have progressed markedly, 2 cardiovascular disease still constitutes a major and increasing health burden in developed countries. Thus, the development of novel treatments for patients with cardiovascular diseases remains a major research priority.…”

mentioning

confidence: 99%

Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease

Minamino

Komuro

Kitakaze

2010

Circulation Research

415

347

View full text Add to dashboard Cite

Cardiovascular disease constitutes a major and increasing health burden in developed countries.Although treatments have progressed, the development of novel treatments for patients with cardiovascular diseases remains a major research goal. The endoplasmic reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins lead to the accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers the unfolded protein response (UPR) to maintain ER homeostasis. The UPR involves a group of signal transduction pathways that ameliorate the accumulation of unfolded protein by increasing ER-resident chaperones, inhibiting protein translation and accelerating the degradation of unfolded proteins. The UPR is initially an adaptive response but, if unresolved, can lead to apoptotic cell death. Thus, the ER is now recognized as an important organelle in deciding cell life and death. There is compelling evidence that the adaptive and proapoptotic pathways of UPR play fundamental roles in the development and progression of cardiovascular diseases, including heart failure, ischemic heart diseases, and atherosclerosis. Thus, therapeutic interventions that target molecules of the UPR component and reduce ER stress will be promising strategies to treat cardiovascular diseases. In this review, we summarize the recent progress in understanding UPR signaling in cardiovascular disease and its related therapeutic potential. Future studies may clarify the most promising molecules to be investigated as targets for cardiovascular diseases. (Circ Res. 2010;107:1071-1082.) Key Words: heart failure Ⅲ ischemic heart diseases Ⅲ atherosclerosis Ⅲ ER stress Ⅲ unfolded protein response A lthough the clinical management of heart failure has advanced substantially, 1 and prevention strategies for atherosclerosis focused on managing the established risk factors have progressed markedly, 2 cardiovascular disease still constitutes a major and increasing health burden in developed countries. Thus, the development of novel treatments for patients with cardiovascular diseases remains a major research priority.The endoplasmic reticulum (ER) comprises a complex membranous network found in all eukaryotic cells. It plays a crucial role in the folding of secretory and membrane proteins, calcium homeostasis, and lipid biosynthesis. 3-5 ER Original

show abstract

“…[16][17][18] Therefore, it is difficult to extrapolate from these studies the appropriate treatment for asymptomatic patients who are at risk of developing HF, such as those with diabetes, previous myocardial infarction, atrial fibrillation, obesity, metabolic syndrome, peripheral vascular disease, and increasing age. 19 The present work evaluates the To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after β-blockade in SCH.…”

mentioning

confidence: 99%

Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Crespo

Cruz

Altieri

et al. 2008

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.

show abstract

The Year in Heart Failure

Cited by 9 publications

References 111 publications

Serum intact parathyroid hormone levels predict hospitalisation for heart failure

Serum intact parathyroid hormone levels predict hospitalisation for heart failure

Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease

Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Contact Info

Product

Resources

About