Review
Peripheral Vascular Disease
Susan M. Wall
Summary: Intercalated cells play a crucial role in acid-base balance by secreting H+ or HCO3- and mediating Cl- absorption and HCO3- secretion through pendrin-mediated anion exchange. They also indirectly regulate blood pressure through pendrin-mediated Cl- absorption and their effect on the epithelial Na+ channel.
Article
Endocrinology & Metabolism
Arthur D. D. Zimmerman, Laci Mackay, Robert J. J. Kemppainen, Melaney A. A. Jones, Casey C. C. Read, Dean Schwartz, Chad D. D. Foradori
Summary: Atrazine treatment and stressed animals both exhibit reduced thickness of the adrenal zona glomerulosa and expression of aldosterone synthase, indicating repeated stimulation of the adrenal glands. Atrazine-treated animals show higher circulating aldosterone levels compared to stressed and control animals, demonstrating increased production of aldosterone independent of changes in the expression of steroidogenic enzymes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Peripheral Vascular Disease
Juhong Zhang, Yuqing Zhang, Jing Gao, Meihui Wang, Xiaoting Li, Zhaoqiang Cui, Guosheng Fu
Summary: The study revealed that the long noncoding RNA Tug1 plays a critical role in renal fibrosis by competitively regulating miR-29b-3p and extracellular matrix gene expression. Furthermore, mineralocorticoid receptor may mediate the regulation of miR-29b-3p through modulating Tug1 expression, thus influencing the occurrence of renal fibrosis.
Article
Physiology
Ebrahim Tahaei, Truyen D. Pham, Lama Al-Qusairi, Rick Grimm, Susan M. Wall, Paul A. Welling
Summary: The Cl-/HCO3- exchanger pendrin in the kidney regulates acid-base balance and intravascular volume. Its expression is differentially regulated by different dietary potassium salts, with high-KHCO3 diet increasing pendrin abundance and high-KCl diet decreasing it. The regulation of pendrin is prioritized by the accompanying anion to prevent metabolic alkalosis or hyperchloremic acidosis.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Yusuf Ali, Elise P. Gomez-Sanchez, Celso E. Gomez-Sanchez
Summary: The mTOR signaling pathway plays a crucial role in transducing the AngII signal initiating aldosterone and cortisol synthesis in HAC15 cells.
Article
Biochemistry & Molecular Biology
Youyou Li, Hongxing Li, Wenjuan Xing, Jianwei Li, Ruikai Du, Dengchao Cao, Yinbo Wang, Xueyi Yang, Guohui Zhong, Yinlong Zhao, Weijia Sun, Caizhi Liu, Xingcheng Gao, Yeheng Li, Zizhong Liu, Xiaoyan Jin, Dingsheng Zhao, Yingjun Tan, Yanqing Wang, Shujuan Liu, Min Yuan, Jinping Song, Yan-Zhong Chang, Feng Gao, Shukuan Ling, Yingxian Li
Summary: The knockout of miR-214 in VSMCs significantly alleviates Ang II-induced hypertension, reduces systolic blood pressure, inhibits vascular medial thickness, blunts the response of blood vessels to various stimuli, and reverses vascular dysfunction. The mechanism involves a crosstalk between AT1R signaling and TGF-beta/Smad signaling pathways. The results suggest that miR-214 could be a potential therapeutic target for hypertension treatment.
Article
Immunology
Ikram Omar Osman, Clea Melenotte, Philippe Brouqui, Matthieu Million, Jean-Christophe Lagier, Philippe Parola, Andreas Stein, Bernard La Scola, Line Meddeb, Jean-Louis Mege, Didier Raoult, Christian A. Devaux
Summary: SARS-CoV-2 infection can lead to variations in ACE2 expression and Ang II plasma concentration, potentially affecting blood pressure regulation and COVID-19 outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chantelle Thimm, Lars Erichsen, Wasco Wruck, James Adjaye
Summary: Podocytes, specialized cells in the kidney, play a crucial role in blood filtration and dysfunction of these cells can lead to renal diseases. Studying and utilizing podocytes is important in the field of regenerative medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Huanhuan Wang, Yuan Tian, Qihe Zhang, Wenyun Liu, Lingbin Meng, Xin Jiang, Ying Xin
Summary: The study suggests that upregulating Nrf2 expression to activate antioxidant stress factors may play a crucial role in protecting against Ang II-induced aortic damage. Sulforaphane (SFN), an Nrf2 agonist, exerts a protective effect through the ERK/GSK-3β/Fyn pathway.
Article
Biochemistry & Molecular Biology
Ilaria Caputo, Brasilina Caroccia, Ilaria Frasson, Elena Poggio, Stefania Zamberlan, Margherita Morpurgo, Teresa M. Seccia, Tito Cali, Marisa Brini, Sara N. Richter, Gian Paolo Rossi
Summary: Blockers of the renin-angiotensin system (RAS) can increase the expression of ACE2, the cellular receptor of SARS-CoV-2, and thus increase the risk of COVID-19. This study found that angiotensin II (Ang II) significantly increased the levels of ACE2 expression by acting on the angiotensin type 1 receptor, resulting in enhanced viral entry into cells. However, the blockade of ACE-1-mediated Ang II formation and ACE2-mediated Ang II conversion did not have any effect. Therefore, increased production of Ang II in patients with an activated RAS may lead to a greater spread of COVID-19 infection in lung cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Rasmus Dreier, Ulrik B. Andersen, Julie L. Forman, Majid Sheykhzade, Martin Egfjord, Jorgen L. Jeppesen
Summary: Increasing potassium intake raises plasma potassium and aldosterone levels, potentiating AngII-stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Oncology
Bing Zhou, Nan Wu, Yuan Yan, Lu-Lu Wu, Guo-Qing Zhu, Xiao-Qing Xiong
Summary: This study demonstrates that the upregulation of miR-31-5p and the downregulation of FNDC5 contribute to Ang II-induced VSMC proliferation and migration.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Richard Perryman, Alexander Renziehausen, Hamidreza Shaye, Androniki D. Kostagianni, Antonis D. Tsiailanis, Thomas Thorne, Maria Chatziathanasiadou, Gregory B. Sivolapenko, Mohamed Ahmed El Mubarak, Gye Won Han, Barbara Zarzycka, Vsevolod Katritch, Guillaume Lebon, Cristiana Lo Nigro, Laura Lattanzio, Sophie Morse, James J. Choi, Kevin O'Neill, Zoi Kanaki, Apostolos Klinakis, Tim Crook, Vadim Cherezov, Andreas G. Tzakos, Nelofer Syed
Summary: This study reveals that AT(2)R is a therapeutic target for GBM and AngII promotes proliferation through this receptor. EMA401 and its derivative A3E can inhibit the proliferation and invasiveness of GBM, and show enhanced penetration in the CNS.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Wanessa M. C. Awata, Arthur H. Sousa, Marcela M. B. de Mello, Thales M. H. Dourado, Lucas C. Pinheiro, Jefferson Elias-Oliveira, Vanessa F. Rodrigues, Daniela Carlos, Michele M. Castro, Carlos R. Tirapelli
Summary: Ethanol consumption leads to dysfunction of perivascular adipose tissue (PVAT) through the activation of the renin-angiotensin-aldosterone system (RAAS), particularly through the involvement of angiotensin II type 1 receptors (AT1R). This dysfunction involves reductions in the production of adiponectin and nitric oxide, resulting in impaired vasodilation and increased vascular contraction. These findings suggest that PVAT dysfunction may contribute to the hypertensive effects associated with ethanol consumption.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dinesh Aryal, Tithi Roy, Jean Christopher Chamcheu, Keith E. Jackson
Summary: This study found that chronic metabolic acidosis induced in Sprague Dawley rats led to sustained elevation in blood pressure and significant decrease in blood pH. Treatment with captopril/tempol resulted in a significant decrease in blood pressure, while spironolactone did not show the same effect. Induction of chronic acidosis may potentially be causative of hypertension, possibly through activation of intrarenal angiotensin II and induction of oxidative stress.
Review
Medicine, General & Internal
Kohei Odajima, Ryo Togashi, Yoshikazu Nemoto, Yuto Hayama, Shinichiro Asakawa, Michito Nagura, Shigeyuki Arai, Osamu Yamazaki, Yoshifuru Tamura, Makoto Mochizuki, Ryuji Ohashi, Shigeru Shibata, Yoshihide Fujigaki
Summary: The article discusses a case of acute pyelonephritis leading to acute kidney injury, describing its clinical presentation, pathological features, and treatment process. The idea that NSAID use may be a potential risk factor is proposed.
Review
Urology & Nephrology
Nobuhiro Ayuzawa, Toshiro Fujita
Summary: Hypertension and its comorbidities are major public health concerns related to modern lifestyle factors. Aldosterone and its receptor, MR, play crucial roles in salt-sensitive hypertension and renal injuries. Obesity-related overproduction of aldosterone and ligand-independent signaling are identified as novel mechanisms of MR activation.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Review
Urology & Nephrology
Wakako Kawarazaki, Toshiro Fujita
Summary: This review discusses the impact of adverse environmental factors such as prenatal malnutrition, obesity, and aging on salt-sensitive hypertension, as well as the underlying mechanisms. Kidney mechanisms and aberrant DNA methylation of certain genes play crucial roles in the development of this condition.
NATURE REVIEWS NEPHROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Wakako Kawarazaki, Toshiro Fujita
Summary: High salt intake can result in increased blood pressure, especially in individuals with impaired renal sodium excretion, leading to salt-sensitive hypertension. Activation of Rho in the central nervous system and vascular smooth muscle cells plays a crucial role in this process, contributing to increased vascular resistance and tone, ultimately impacting blood pressure control.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Peripheral Vascular Disease
Daigoro Hirohama, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Wakako Kawarazaki, Wataru Fujii, Shigeyoshi Oba, Shigeru Shibata, Takeshi Marumo, Toshiro Fujita
Summary: The study revealed that the activation of the Rac1-MR pathway contributes to the progression of DKD by causing hypertension and podocyte injury, highlighting MR antagonism and Rac1 inhibition as a novel strategy for DKD treatment.
Article
Peripheral Vascular Disease
Fumika Ochiai-Homma, Emiko Kuribayashi-Okuma, Yuya Tsurutani, Kenichi Ishizawa, Wataru Fujii, Kohei Odajima, Mika Kawagoe, Yoshihiro Tomomitsu, Masataka Murakawa, Shinichiro Asakawa, Daigoro Hirohama, Michito Nagura, Shigeyuki Arai, Osamu Yamazaki, Yoshifuru Tamura, Yoshihide Fujigaki, Tetsuo Nishikawa, Shigeru Shibata
Summary: The study demonstrates the correlation between pendrin levels in uEVs and human PA, suggesting that therapeutic interventions can attenuate pendrin abundance in patients with PA. The analysis of pendrin in uEVs, along with other proteins, may be useful in understanding the pathophysiology of hypertensive disorders.
HYPERTENSION RESEARCH
(2021)
Editorial Material
Urology & Nephrology
Daigoro Hirohama, Katalin Susztak
Summary: In 2021, significant progress was made in understanding the genetics of kidney function and disease, with key advances in genome-wide association studies and multi-omics methods identifying key genes and cell types involved in disease development.
NATURE REVIEWS NEPHROLOGY
(2022)
Review
Peripheral Vascular Disease
Atsuhisa Sato, Mitsuhiro Nishimoto
Summary: This article summarizes the latest evidence on the use of nonsteroidal MR antagonists in the treatment of diabetic kidney disease (DKD). It highlights the effectiveness of MR antagonists and suggests measures for managing hyperkalemia. The study emphasizes the importance of continuous use of MR antagonists in DKD treatment.
HYPERTENSION RESEARCH
(2022)
Review
Peripheral Vascular Disease
Toshiro Fujita
Summary: This review focuses on the epigenetic mechanism of salt-sensitive hypertension, particularly through DNA methylation and histone modification-mediated regulation of hypertension-associated genes. It discusses how maternal malnutrition and lipopolysaccharide exposure during pregnancy can lead to the development of salt-induced hypertension in future generations by upregulating certain genes. In mice, aberrant DNA methylation of the Klotho gene is also shown to contribute to the development of salt-sensitive hypertension. Understanding these epigenetic modulations could provide valuable insights for developing preventive and therapeutic approaches to hypertension.
Review
Biochemistry & Molecular Biology
Wataru Fujii, Shigeru Shibata
Summary: This article reviews the extensive research conducted over the past 80 years on the regulation and action of the mineralocorticoid receptor (MR). It highlights the role of MR and the steroid hormone aldosterone in integrating responses of tubular cells and maintaining fluid homeostasis, as well as their dysregulation in kidney diseases. Experimental studies have shown the pathological consequences of MR overactivity and the mechanisms of enhanced MR signaling, while clinical studies have demonstrated the renoprotective effects of MR blockade. The article also discusses future areas of investigation, including the use of non-steroidal MR antagonists in non-diabetic kidney disease patients and the search for downstream mediators of renoprotection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Daigoro Hirohama, Amin Abedini, Salina Moon, Aditya Surapaneni, Simon T. Dillon, Allison Vassalotti, Hongbo Liu, Tomohito Doke, Victor Martinez, Zaipul Md Dom, Anil Karihaloo, Matthew B. Palmer, Josef Coresh, Morgan E. Grams, Monika A. Niewczas, Katalin Susztak
Summary: In this study, unbiased proteomics analysis was performed to identify diagnostic markers for kidney fibrosis and future kidney function decline in patients with diabetic kidney disease (DKD). It was found that matrix metalloprotease 7 (MMP7) is significantly associated with both fibrosis in renal tissue and decline in kidney function. Additionally, plasma levels of MMP7 were found to correlate with future kidney function decline.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Peripheral Vascular Disease
Benjamin Bonnard, Soumaya El Moghrabi, Kohei Ueda, Lionel Lattenist, Matthieu Soulie, Natalia Lopez-Andres, Constance Xhaard, Tatsuo Shimosawa, Patrick Rossignol, Frederic Jaisser
Summary: Our study highlights the correlation between NGAL/lcn2 with blood pressure and urinary sodium excretion, and its important role in salt-sensitive hypertension. NGAL/lcn2 modulates the activity of the renal sodium transporter NCC, thereby affecting sodium balance and blood pressure control.