Insights Into the Activation and Inhibition of Angiotensin II Type 1 Receptor in the Mechanically Loaded Heart

Wu, Jian; You, J. Q.; Wang, Shijun; Zhang, Li; Gong, Hui; Zou, Yunzeng

doi:10.1253/circj.cj-14-0470

Cited by 29 publications

(29 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, whether CTSB affects chronic pressure overload-induced cardiac remodeling has never been examined. It is known that pressure overload can activate the renin-angiotensin system and induced the release of ANG II, which activates the G␣ (q) protein-coupled receptor signaling pathway (37). Thus ANG II was used in vitro to induce the cardiac remodeling in cardiomyocytes.…”

mentioning

confidence: 99%

Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway

Yuan

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Cathepsin B (CTSB), a member of the lysosomal cathepsin family that is expressed in both murine and human hearts, was previously shown to participate in apoptosis, autophagy, and the progression of certain types of cancers. Recently, CTSB has been linked to myocardial infarction. Given that cathepsin L, another member of the lysosomal cathepsin family, ameliorates pathological cardiac hypertrophy, we hypothesized that CTSB plays a role in pressure overload-induced cardiac remodeling. Here we report that CTSB was upregulated in cardiomyocytes in response to hypertrophic stimuli both in vivo and in vitro. Moreover, knockout of CTSB attenuated pressure overload-induced cardiac hypertrophy, fibrosis, dysfunction, and apoptosis. Furthermore, the aortic banding-induced activation of TNF-α, apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinases (JNK), c-Jun, and release of cytochrome c was blunted by CTSB deficiency, which was further confirmed in in vitro studies induced by angiotensin II. In cardiomyocytes pretreatment with SP600125, a JNK inhibitor, suppressed the cardiomyocytes hypertrophy by inhibiting the ASK1/JNK pathway. Altogether, these data indicate that the CTSB protein functions as a necessary modulator of hypertrophic response by regulating TNF-α/ASK1/JNK signaling pathway involved in cardiac remodeling.

show abstract

mentioning

confidence: 99%

Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway

Yuan

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…There is compelling evidence that the AT1R may also be activated by mechanical stress without the involvement of Angiotensin II (ref. 21 ). The AT1R is the first recognized mechanosensitive GPCR (ref.…”

Section: Discussionmentioning

confidence: 99%

The impact of Angiotensin II Type 1 Receptor antibodies on morbidity and mortality in Heart Mate II supported recipients

Urban¹,

Slavčev²,

Gazdic³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

, Peter Ivak a , Ivan Netuka a Aims. One of the proposed limitations of left ventricular assist device (LVAD) therapy is high degree of sensitization. Apart from human leukocyte antigen (HLA), antibodies against Angiotensin II Type 1 Receptor (AT1R) have been associated with adverse outcomes. The purpose of this study was to compare complications and survival of anti -AT1R positive versus negative Heart Mate II (HMII) recipients. Methods. Altogether 96 patients received HMII at our institution between 2008 and 2012. These were stratified into three groups: antibody positive before implantation (AT1R+), antibody conversion during support (AT1R-/+) and patients who remained antibody negative (AT1R-). Survival, major on-device adverse events and post-transplant rejections were assessed with Kaplan-Meier and log-rank tests.Results. Two year on-device and overall survival was 78 ± 12% and 75 ± 10% in AT1R-, 60 ± 23% and 60 ± 15% in AT1R+ and 92 ± 6% and 87 ± 5% in AT1R-/+ group (P = 0.409, P = 0.185). Freedom from major adverse event at two years for AT1R-, AT1R+ and AT1R-/+ was 49 ± 14%, 53 ± 16% and 41 ± 11% (P = 0.875). Freedom from rejection was 63 ± 17% in patients who were both anti-AT1R and HLA negative and 65 ± 13% in those who were antibody positive (P = 0.788). Conclusion.Patients who were anti-AT1R antibody positive had similar on-device survival and rate of complications in comparison to those who were antibody negative. In transplanted patients, there were no differences in the overall survival and rejection between the groups.

show abstract

“…33 Vasoconstriction and other downstream effects attributed to the AT1 receptor depend on G-protein pathways. However, additional AT1 receptor signaling pathways involving β-arrestin-1 and -2 exist.…”

Section: Trv027: a Biased Ligandmentioning

confidence: 99%

Novel Therapies for Heart Failure　– Where Do They Stand? –

Greenberg

2016

Circ J

View full text Add to dashboard Cite

Despite advances in therapy, patients with heart failure (HF) continue to experience unacceptably high rates of hospitalization and death, as well as poor quality of life. As a consequence, there is an urgent need for new treatments that can improve the clinical course of the growing worldwide population of HF patients. Serelaxin and ularatide, both based on naturally occurring peptides, have potent vasodilatory as well as other effects on the heart and kidneys. For both agents, phase 3 studies that are designed to determine whether they improve outcomes in patients with acute HF have completed enrollment. TRV027, a biased ligand for the type 1 angiotensin receptor with effects that extend beyond traditional angiotensin-receptor blockers is also being studied in the acute HF population. Omecamtiv mecarbil, an inotropic agent that improves myocardial contractility by a novel mechanism, and vericiguat, a drug that stimulates soluble guanylate cyclase, are both being developed to treat patients with chronic HF. Finally, despite the negative results of the CUPID study, gene transfer therapy continues to be explored as a means of improving the function of the failing heart. The basis for the use of these drugs and their current status in clinical trials are discussed. (Circ J 2016; 80: 1882 -1891

show abstract

Insights Into the Activation and Inhibition of Angiotensin II Type 1 Receptor in the Mechanically Loaded Heart

Cited by 29 publications

References 56 publications

Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway

Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway

The impact of Angiotensin II Type 1 Receptor antibodies on morbidity and mortality in Heart Mate II supported recipients

Novel Therapies for Heart Failure　– Where Do They Stand? –

Contact Info

Product

Resources

About

Insights Into the Activation and Inhibition of Angiotensin II Type 1 Receptor in the Mechanically Loaded Heart

Cited by 29 publications

References 56 publications

Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway

Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway

The impact of Angiotensin II Type 1 Receptor antibodies on morbidity and mortality in Heart Mate II supported recipients

Novel Therapies for Heart Failure – Where Do They Stand? –

Contact Info

Product

Resources

About

Novel Therapies for Heart Failure　– Where Do They Stand? –