Article
Biochemistry & Molecular Biology
Ratchanee Duangrat, Warisara Parichatikanond, Supachoke Mangmool
Summary: Angiotensin II upregulates TGF-beta 1 and ET-1, which act as profibrotic mediators. The signal transduction of ATR for upregulation of TGF-beta 1 and ET-1, and their effectors in myofibroblast differentiation, is not fully understood. In this study, the ATR networking with TGF-beta 1 and ET-1 was investigated, and the signal transduction of these mediators was identified. The findings suggest that TGF-beta 1 and ET-1 are major effectors of the ATR cascade and negative regulation of their signaling represents a targeted therapeutic strategy for cardiac fibrosis prevention and restoration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Jingjing Xu, Xiaohua Jiang, Suowen Xu
Summary: Hypertension is a global epidemic and resistant hypertension affects 15% of patients despite antihypertensive medication. Endothelin-1 plays a crucial role in blood pressure regulation and recent research highlights the potential of aprocitentan, a dual endothelin-1 receptor antagonist, in lowering blood pressure in individuals with resistant hypertension.
DRUG DISCOVERY TODAY
(2023)
Article
Nutrition & Dietetics
Francisca Isabel Bravo, Enrique Calvo, Rafael A. Lopez-Villalba, Cristina Torres-Fuentes, Begona Muguerza, Almudena Garcia-Ruiz, Diego Morales
Summary: Hypertension is a major contributor to premature deaths worldwide and can be prevented by managing cardiovascular diseases. Protein hydrolysates containing antihypertensive peptides derived from agri-food industry byproducts, such as chicken slaughterhouse byproducts, have shown potential in lowering blood pressure. These byproducts, including blood, bones, skins, and chicken feet, have been used to produce protein hydrolysates with angiotensin-converting enzyme (ACE) inhibitory activity. Mechanisms underlying their effects include increased levels of antioxidant compounds, reduced ACE activity, and improved endothelial dysfunction associated with hypertension. However, further clinical studies are needed to confirm these antihypertensive properties and enhance the value of these byproducts in the circular economy model of slaughterhouses.
Review
Cardiac & Cardiovascular Systems
Emily K. McCoy, Katelin M. Lisenby
Summary: Treatment-resistant hypertension (TRH) is associated with increased cardiovascular risks and progression of chronic kidney disease. Aprocitentan, a novel dual endothelin-receptor antagonist, has shown promising results in early clinical trials for TRH patients, demonstrating significant blood pressure reduction and improved tolerability compared to other antagonists. Ongoing phase 3 trials will further evaluate its efficacy and safety.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Ziwei Fu, Fei Wang, Xiyang Liu, Jiajia Hu, Jiahui Su, Xiaohan Lu, Aihua Lu, Jae Min Cho, J. David Symons, Chang-Jiang Zou, Tianxin Yang
Summary: This study demonstrates that sPRR acts as a ligand of the AT1R, contributing to endothelial dysfunction and arterial dysfunction, as well as elevated blood pressure in obese mice. Inhibiting sPRR signaling through the AT1R may be a potential therapeutic intervention for cardiovascular disorders involving hypertension.
Article
Hematology
Julian Kamhieh-Milz, Lei Chen, Claudia Goettsch, Anna Maria Pfefferkorn, Anja Hofmann, Coy Brunssen, Gregor M. Mueller, Thomas Walther, Muhammad Imtiaz Ashraf, Guido Moll, Henning Morawietz, Janusz Witowski, Rusan Catar
Summary: This study analyzed the mechanism by which NOX2 contributes to Ang II-induced ET-1 production in human microvascular endothelial cells. The results showed that high-fat diet increased the expression of Ang II and ET-1 in wild-type mice, but not in Nox2-deficient mice. In vitro experiments revealed that Ang II promoted NOX2 expression through induction of the Oct-1 protein and increased production of superoxide anions. Inhibition of Oct-1 and superoxide attenuated Ang II-induced ET-1 production.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Nutrition & Dietetics
Celeste Trejo-Moreno, Zimri Aziel Alvarado-Ojeda, Marisol Mendez-Martinez, Mario Ernesto Cruz-Munoz, Gabriela Castro-Martinez, Gerardo Arrellin-Rosas, Alejandro Zamilpa, Jesus Enrique Jimenez-Ferrer, Juan Carlos Baez Reyes, Gladis Fragoso, Gabriela Rosas Salgado
Summary: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension and improving tissue damage associated with endothelial dysfunction, probably through Akt activation.
Review
Peripheral Vascular Disease
Sayeh Heidari Nejad, Omar Azzam, Markus P. Schlaich
Summary: Resistant hypertension is associated with increased cardiovascular and renal events, and endothelin antagonists could be a potential alternative fourth-line therapy. Recent research on the dual endothelin antagonist Aprocitentan has shown its safety and efficacy in lowering blood pressure.
CURRENT HYPERTENSION REPORTS
(2023)
Article
Peripheral Vascular Disease
Zhennan Lin, Xinyan Wang, Fangchao Liu, Xueli Yang, Qiong Liu, Xiaolong Xing, Jie Cao, Jianxin Li, Keyong Huang, Weili Yan, Tingting Liu, Meng Fan, Wei Li, Shufeng Chen, Xiangfeng Lu, Dongfeng Gu, Jianfeng Huang
Summary: Short-term exposure to PM2.5 has adverse effects on blood pressure, but these effects are attenuated in patients with controlled blood pressure. Among those with uncontrolled blood pressure, the use of angiotensin receptor blockers may potentially lower blood pressure in response to PM2.5 exposure.
Review
Biochemistry & Molecular Biology
Qiannan Gao, Li Xu, Jun Cai
Summary: Hypertension is a common cardiovascular disease globally, with resistant hypertension being difficult to control effectively. Current antihypertensive drugs may have adverse effects, highlighting the need for new therapeutic targets and treatments to manage hypertension and its comorbidities.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Zheng-Da Pang, Xia Sun, Ru-Yue Bai, Meng-Zhuan Han, Yong-Jian Zhang, Wei Wu, Yu Zhang, Bao-Chang Lai, Yi Zhang, Yan Wang, Xiao-Jun Du, Xiu-Ling Deng
Summary: This study found that vascular endothelial dysfunction is an early event in hypertension, and that Ang II upregulates Gal-3 expression in vascular endothelium by increasing YAP nuclear localization, resulting in endothelial dysfunction and the development of hypertension.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Zeyu Zhang, Chunlei Liu, Yongyi Bai, Xin Li, Xiaojian Gao, Chen Li, Ge Guo, Si Chen, Mingzhuang Sun, Kang Liu, Yang Li, Kunlun He
Summary: A novel endothelin receptor antagonist, pipersentan, has been synthesized and shown to effectively treat ET-1 system activation-related pulmonary arterial hypertension, making it a potential new therapeutic agent.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ruiqi Liu, Tianyi Yuan, Ranran Wang, Difei Gong, Shoubao Wang, Guanhua Du, Lianhua Fang
Summary: This paper reviews the regulation of endothelin receptors and their pathways in normal physiological processes and disease processes, and describes the mechanistic roles of ET receptor antagonists that are currently approved and used in clinical studies. Current clinical researches on ET are focused on the development of multi-target combinations and novel delivery methods to improve efficacy and patient compliance while reducing side effects. Future research directions and trends of ET targets, including monotherapy and precision medicine, are also described in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Katsutoshi Tokushige, Tomomi Kogiso, Hiroto Egawa
Summary: Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Early diagnosis of PoPH and prompt initiation of therapy with PAH-specific drugs is important for achieving good treatment outcomes. Measurement of serum brain natriuretic peptide levels may be useful for detecting PoPH. Liver transplantation (LT) was previously contraindicated for PoPH, but the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Peripheral Vascular Disease
Parisa Danaietash, Pierre Verweij, Ji-Guang Wang, George Dresser, Ilkka Kantola, Mary Katherine Lawrence, Krzysztof Narkiewicz, Markus Schlaich, Marc Bellet
Summary: The PRECISION study explores the impact of the dual endothelin receptor antagonist aprocitentan on blood pressure in patients with resistant hypertension. The study is designed in three parts to assess the short-term and sustained long-term effects of aprocitentan. Results are expected in 2022. The study found a high proportion of pseudoresistant hypertension among the included patients.
JOURNAL OF CLINICAL HYPERTENSION
(2022)