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JOURNAL ARTICLE
Lashodya V Dissanayake, Oleg Palygin, Alexander Staruschenko
PURPOSE OF REVIEW: Salt-sensitive (SS) hypertension and its associated kidney damage have been extensively studied, yet proper therapeutic strategies are lacking. The interest in altering the metabolome to affect renal and cardiovascular disease has been emerging. Here, we discuss the effect and potential mechanism behind the protective effect of lysine, an essential amino acid, on the progression of SS hypertension. RECENT FINDINGS: We have recently demonstrated that administering lysine in an SS rodent model can control the progression of hypertension...
April 22, 2024: Current Opinion in Nephrology and Hypertension
#2
JOURNAL ARTICLE
Wenxing Wu, Rui Liu, Sheng Guo, Wencong Song, Yongqing Hua, Min Hong, Jie Zheng, Yue Zhu, Peng Cao, Jin-Ao Duan
ETHNOPHARMACOLOGICAL RELEVANCE: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. AIM OF THE STUDY: The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension...
April 16, 2024: Journal of Ethnopharmacology
#3
JOURNAL ARTICLE
Xianxian Liu, Xiaoming Zeng, Xing Li, Siming Xin, Feng Zhang, Faying Liu, Yang Zeng, Jilin Wu, Yang Zou, Xinwei Xiong
BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome...
April 17, 2024: Journal of Translational Medicine
#4
JOURNAL ARTICLE
Xiaopeng Yin, Changhao Duan, Lin Zhang, Yufang Zhu, Yueyao Qiu, Kaiyi Shi, Sen Wang, Xiaoguang Zhang, Huaxing Zhang, Yinchao Hao, Fang Yuan, Yanming Tian
BACKGROUND: Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear. METHODS: The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry...
April 18, 2024: Journal of Neuroinflammation
#5
JOURNAL ARTICLE
Jinxia Liu, Jane MacNaughtan, Annarein J C Kerbert, Theo Portlock, Javier Martínez Gonzalez, Yi Jin, Frederick Clasen, Abeba Habtesion, Huoyan Ji, Qin Jin, Alexandra Phillips, Francesco De Chiara, Ganesh Ingavle, Cesar Jimenez, Giacomo Zaccherini, Katherine Husi, Miguel Angel Rodriguez Gandia, Paul Cordero, Junpei Soeda, Lynda McConaghy, Jude Oben, Karen Church, Jia V Li, Haifeng Wu, Aarti Jalan, Pere Gines, Elsa Solà, Simon Eaton, Carrie Morgan, Michal Kowalski, Daniel Green, Amir Gander, Lindsey A Edwards, I Jane Cox, Helena Cortez-Pinto, Thomas Avery, Reiner Wiest, Francois Durand, Paolo Caraceni, Roberto Elosua, Joan Vila, Marco Pavesi, Vicente Arroyo, Nathan Davies, Rajeshwar P Mookerjee, Victor Vargas, Susan Sandeman, Gautam Mehta, Saeed Shoaie, Julian Marchesi, Agustín Albillos, Fausto Andreola, Rajiv Jalan
OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro . Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied...
April 15, 2024: Gut
#6
REVIEW
Martina Lombardi, Jacopo Troisi, Benedetta Maria Motta, Pietro Torre, Mario Masarone, Marcello Persico
Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH...
April 1, 2024: Nutrients
#7
JOURNAL ARTICLE
Wenhua Li, Pengfei Wu, Tianrong Jin, Jialin Jia, Bo Chen, Tingting Liu, Yu Liu, Jie Mei, Bangwei Luo, Zhiren Zhang
Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice...
2024: Frontiers in Immunology
#8
MULTICENTER STUDY
Robin Knuchel, Zoran Erlic, Sven Gruber, Laurence Amar, Casper K Larsen, Anne-Paule Gimenez-Roqueplo, Paolo Mulatero, Martina Tetti, Alessio Pecori, Christina Pamporaki, Katharina Langton, Mirko Peitzsch, Filippo Ceccato, Aleksander Prejbisz, Andrzej Januszewicz, Christian Adolf, Hanna Remde, Livia Lenzini, Michael Dennedy, Jaap Deinum, Emily Jefferson, Anne Blanchard, Maria-Christina Zennaro, Graeme Eisenhofer, Felix Beuschlein
INTRODUCTION: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT...
2024: Frontiers in Endocrinology
#9
JOURNAL ARTICLE
Mateusz Dziedzic, Ewelina Józefczuk, Tomasz J Guzik, Mateusz Siedlinski
BACKGROUND: Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension (HTN) and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. METHODS: The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD...
April 8, 2024: Hypertension
#10
JOURNAL ARTICLE
Zihan Wang, Chu-Fan Wang, Hongbing Fan, Xiaoyu Bao, Fatemeh Ashkar, Liang Li, Tony K L Kiang, Jianping Wu
Peptide IRW is the first food-derived angiotensin-converting enzyme 2 (ACE2) upregulator. This study aimed to investigate the pharmacokinetic characteristics of IRW and identify the metabolites contributing to its antihypertensive activity in spontaneously hypertensive rats (SHRs). Rats were administered 100 mg of IRW/kg of the body weight via an intragastric or intravenous route. The bioavailability ( F %) was determined to be 11.7%, and the half-lives were 7.9 ± 0.5 and 28.5 ± 6.8 min for gavage and injection, respectively...
April 6, 2024: Journal of Agricultural and Food Chemistry
#11
JOURNAL ARTICLE
Yu-Jing Chen, Han-Fei Li, Fan-Rong Zhao, Miao Yu, Si-Yu Pan, Wen-Ze Sun, Yan-Yan Yin, Tian-Tian Zhu
Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model...
March 28, 2024: International Immunopharmacology
#12
JOURNAL ARTICLE
Yasmin Sultana, Damanpreet Kaur Lang, Thomson Santosh Alex, Rakhi Khabiya, Akanksha Dwivedi, Saikat Sen, Raja Chakraborty
Overproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions...
February 15, 2024: Cardiovascular & Hematological Agents in Medicinal Chemistry
#13
JOURNAL ARTICLE
Luis Carlos López-Romero, José Jesús Broseta, Marta Roca-Marugán, Juan R Muñoz-Castañeda, Agustín Lahoz, Julio Hernández-Jaras
X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension...
March 21, 2024: International Journal of Molecular Sciences
#14
RANDOMIZED CONTROLLED TRIAL
Catarina Santos, Rui Carvalho, Ana Mafalda Fonseca, Miguel Castelo Branco, Marco Alves, Ivana Jarak
In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication...
March 18, 2024: International Journal of Molecular Sciences
#15
JOURNAL ARTICLE
Inés García-Lunar, Inmaculada Jorge, Jorge Sáiz, Núria Solanes, Ana Paula Dantas, Juan José Rodríguez-Arias, María Ascaso, Carlos Galán-Arriola, Francisco Rafael Jiménez, Elena Sandoval, Jorge Nuche, Maria Moran-Garrido, Emilio Camafeita, Montserrat Rigol, Javier Sánchez-Gonzalez, Valentín Fuster, Jesús Vázquez, Coral Barbas, Borja Ibáñez, Daniel Pereda, Ana García-Álvarez
Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group...
March 27, 2024: Basic Research in Cardiology
#16
JOURNAL ARTICLE
Lanfranco D'Elia, Maria Masulli, Pietro Cirillo, Agostino Virdis, Edoardo Casiglia, Valerie Tikhonoff, Fabio Angeli, Carlo Maria Barbagallo, Michele Bombelli, Federica Cappelli, Rosario Cianci, Michele Ciccarelli, Arrigo F G Cicero, Massimo Cirillo, Raffaella Dell'Oro, Giovambattista Desideri, Claudio Ferri, Loreto Gesualdo, Cristina Giannattasio, Guido Grassi, Guido Iaccarino, Luciano Lippa, Francesca Mallamaci, Alessandro Maloberti, Stefano Masi, Alberto Mazza, Alessandro Mengozzi, Maria Lorenza Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Roberto Pontremoli, Fosca Quarti-Trevano, Marcello Rattazzi, Gianpaolo Reboldi, Giulia Rivasi, Elisa Russo, Massimo Salvetti, Giuliano Tocci, Andrea Ungar, Paolo Verdecchia, Francesca Viazzi, Massimo Volpe, Claudio Borghi, Ferruccio Galletti
Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied ( n = 2230)...
March 14, 2024: Metabolites
#17
JOURNAL ARTICLE
Xiaoguang Xu, Chachrit Khunsriraksakul, James M Eales, Sebastien Rubin, David Scannali, Sushant Saluja, David Talavera, Havell Markus, Lida Wang, Maciej Drzal, Akhlaq Maan, Abigail C Lay, Priscilla R Prestes, Jeniece Regan, Avantika R Diwadkar, Matthew Denniff, Grzegorz Rempega, Jakub Ryszawy, Robert Król, John P Dormer, Monika Szulinska, Marta Walczak, Andrzej Antczak, Pamela R Matías-García, Melanie Waldenberger, Adrian S Woolf, Bernard Keavney, Ewa Zukowska-Szczechowska, Wojciech Wystrychowski, Joanna Zywiec, Pawel Bogdanski, A H Jan Danser, Nilesh J Samani, Tomasz J Guzik, Andrew P Morris, Dajiang J Liu, Fadi J Charchar, Maciej Tomaszewski
Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively)...
March 19, 2024: Nature Communications
#18
JOURNAL ARTICLE
Hung-Yao Ho, Yuan-Ho Chen, Chi-Jen Lo, Hsiang-Yu Tang, Su-Wei Chang, Chun-Ming Fan, Yu-Hsuan Ho, Gigin Lin, Chih-Yung Chiu, Chih-Ming Lin, Mei-Ling Cheng
The coming of the hyper-aged society in Taiwan prompts us to investigate the relationship between the metabolic status of sarcopenic patients and their most adverse outcome-death. We studied the association between any plasma metabolites and the risk for mortality among older Taiwanese sarcopenic patients. We applied a targeted metabolomic approach to study the plasma metabolites of adults aged ≥65 years, and identified the metabolic signature predictive of the mortality of sarcopenic patients who died within a 5...
February 23, 2024: Nutrients
#19
REVIEW
Ioannis Alexandros Charitos, Maria Aliani, Pasquale Tondo, Maria Venneri, Giorgio Castellana, Giulia Scioscia, Francesca Castellaneta, Donato Lacedonia, Mauro Carone
Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one...
February 29, 2024: International Journal of Molecular Sciences
#20
Lloyd D Harvey, Mona Alotaibi, Hee-Jung Janice Kim, Yi-Yin Tai, Ying Tang, Wei Sun, Wadih El Khoury, Chen-Shan C Woodcock, Yassmin Al Aaraj, Claudette M St Croix, Donna B Stolz, Jiyoung Lee, Mary Hongying Cheng, Tae-Hwi Schwantes-An, Ankit A Desai, Michael W Pauciulo, William C Nichols, Amy Webb, Robert Lafyatis, Mehdi Nouraie, Haodi Wu, Jeffrey G McDonald, Caroline Chauvet, Susan Cheng, Ivet Bahar, Thomas Bertero, Raymond L Benza, Mohit Jain, Stephen Y Chan
Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation...
March 1, 2024: bioRxiv
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