Review
Biochemistry & Molecular Biology
Dan Xu, Ya-Hui Hu, Xue Gou, Feng-Yang Li, Xi-Yu-Chen Yang, Yun-Man Li, Feng Chen
Summary: Pulmonary arterial hypertension (PAH) is a clinical condition characterized by progressive increase in pulmonary artery pressure, leading to right ventricular hypertrophy and right heart failure. Oxidative stress plays a critical role in the pathogenesis of PAH, affecting cell proliferation and vascular remodeling. Antioxidant treatment has become a key research area for PAH therapy.
Review
Biochemistry & Molecular Biology
Fabio Bioletto, Martina Bollati, Chiara Lopez, Stefano Arata, Matteo Procopio, Federico Ponzetto, Ezio Ghigo, Mauro Maccario, Mirko Parasiliti-Caprino
Summary: Primary aldosteronism is recognized as the most common cause of secondary hypertension, associated with high-risk phenotypes and increased cardiovascular morbidity. Excessive aldosterone secretion can contribute to the development of hypertension and drug resistance through various mechanisms and worsen end-organ damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jose L. Sanchez-Gloria, Constanza E. Martinez-Olivares, Leonardo Del Valle-Mondragon, Fernando Cortes-Camacho, Oscar R. Zambrano-Vasquez, Rogelio Hernandez-Pando, Fausto Sanchez-Munoz, Laura G. Sanchez-Lozada, Horacio Osorio-Alonso
Summary: In this study, we evaluated the effects of allicin on vascular remodeling, endothelial function, and oxidative stress in experimental pulmonary arterial hypertension (PAH). Allicin administration improved body weight, survival rate, and prevented wall thickness and right ventricle hypertrophy. Allicin also maintained normal levels of angiotensin II and its receptors, increased nitric oxide and other beneficial molecules, and prevented oxidative stress and hypoxia response. These effects of allicin contribute to preventing endothelial dysfunction, remodeling of the pulmonary arteries, and heart failure in PAH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Peripheral Vascular Disease
Fabrizio Buffolo, Jacopo Burrello, Alessio Burrello, Daniel Heinrich, Christian Adolf, Lisa Marie Muller, Rusi Chen, Vittorio Forestiero, Elisa Sconfienza, Martina Tetti, Franco Veglio, Tracy Ann Williams, Paolo Mulatero, Silvia Monticone
Summary: This study developed a scoring system and machine learning algorithms to accurately predict the individual pretest probability of primary aldosteronism (PA) in patients with hypertension, improving diagnostic accuracy and avoiding unnecessary screening for some patients.
Article
Medicine, General & Internal
Manoj Kumar Choudhary, Emmi Varri, Niina Matikainen, Jenni Koskela, Antti J. Tikkakoski, Mika Kahonen, Onni Niemel, Jukka Mustonen, Pasi Nevalainen, Ilkka Porsti
Summary: Medicated PA patients exhibit higher systemic vascular resistance and wave reflection compared to medicated EH patients, but show higher extracellular water volume, cardiac output, and arterial stiffness. Further studies are needed to determine if evaluating these features systematically would benefit the clinical diagnostics of PA.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Cheng-Hsuan Tsai, Che-Wei Liao, Xue-Ming Wu, Zheng-Wei Chen, Chien-Ting Pan, Yi-Yao Chang, Bo-Ching Lee, Chia-Tung Shun, Wen-Fen Wen, Chia-Hung Chou, Vin-Cent Wu, Chi-Sheng Hung, Yen-Hung Lin
Summary: The presence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is associated with worse arterial stiffness and vascular remodeling. Patients with ACS have higher prevalence of diabetes mellitus and more severe vascular fibrosis.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kiyotaka Itcho, Kenji Oki, Haruya Ohno, Masayasu Yoneda
Summary: Primary aldosteronism (PA) is the most common form of secondary hypertension, with two main subtypes: aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism. Recent advancements in genetic analysis have led to the discovery of mutations in causative genes, contributing to a better understanding of the mechanism of excess aldosterone synthesis.
Article
Endocrinology & Metabolism
Ahmed Saadi, Mohamed Ali Bedoui, Selim Zaghbib, Hamza Boussaffa, Seif Mokaddem, Ibtissem Ben Nacef, Haroun Ayed, Amine Derouiche, Karima Khiari, Marouene Chakroun, Riadh Ben Slama
Summary: This study retrospectively analyzed the medical records of 71 Tunisian patients who underwent surgery for UPA. The complete clinical success rate was 48% and the partial clinical success rate was 43%. Absence of diabetes, low BMI, high plasma ARR, and high ARS were identified as the main predictors of complete resolution of hypertension.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Xiaomei Lv, Huijun Hu, Chuyu Shen, Xiaoyun Zhang, Li Yan, Shaoling Zhang, Ying Guo
Summary: This study aimed to explore the risk factors for lower bone mineral density (BMD) in primary aldosteronism (PA) patients. The results showed that PA patients had lower BMD compared to essential hypertension (EH) patients, and this was associated with age, serum phosphorus, urinary calcium excretion, mean platelet volume (MPV), superoxide dismutase (SOD), and total bilirubin (TBIL).
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Nutrition & Dietetics
Niki Mourtzi, Amalia Sertedaki, Athina Markou, George P. Piaditis, Evangelia Charmandari
Summary: Recent genetic studies have made significant progress in understanding primary aldosteronism, with the identification of various mutations associated with both sporadic and familial forms of the disease. The prevalence of PA is higher than previously thought, highlighting the need for improved diagnostic tools and further research to identify milder forms of the condition and explore underlying molecular mechanisms.
Article
Peripheral Vascular Disease
James M. Luther, Dawei S. Wei, Kakali Ghoshal, Dungeng Peng, Gail K. Adler, Adina F. Turcu, Hui Nian, Chang Yu, Carmen C. Solorzano, Ambra Pozzi, Nancy J. Brown
Summary: Epoxyeicosatrienoic acids (EETs) are lipid signaling molecules generated by the action of CYP450s, with vasodilatory, anti-inflammatory, and insulin-enhancing effects. Treatment of primary aldosteronism led to an increase in EET concentrations, particularly 14,15-DHETs.
Review
Biochemistry & Molecular Biology
Hollie Speer, Andrew J. McKune
Summary: Hypertension is a major risk factor for cardiovascular diseases, and studying the factors involved in its progression is crucial for healthy aging. Aging is associated with a loss of skeletal muscle quantity and quality, as well as an increase in Reactive Oxygen and Nitrogen Species, which may accelerate the aging process.
Article
Endocrinology & Metabolism
Daisuke Watanabe, Satoshi Morimoto, Noriko Morishima, Atsuhiro Ichihara
Summary: Patients with primary aldosteronism, particularly those with aldosterone-producing adenoma (APA), demonstrate impaired endothelial function compared to those with essential hypertension. Flow-mediated dilation (FMD) was lower in APA and bilateral idiopathic hyperplasia (IHA) groups, while cardio-ankle vascular index (CAVI) did not significantly differ among the groups. High FMD was associated with blood pressure normalization after adrenalectomy in the APA group.
ENDOCRINE CONNECTIONS
(2021)
Article
Endocrinology & Metabolism
Chun-Kai Chang, Chin-Chen Chang, Vin-Cent Wu, Jiun-Hung Geng, Hsiang-Ying Lee
Summary: This study revealed a strong association between primary aldosteronism (PA) and renal stones, with PA-related renal stones being larger and harder than those in the essential hypertension group.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Peripheral Vascular Disease
Siyuan Gong, Na Sun, Lucie S. Meyer, Martina Tetti, Christina Koupourtidou, Stefan Krebs, Giacomo Masserdotti, Helmut Blum, William E. Rainey, Martin Reincke, Axel Walch, Tracy Ann Williams
Summary: In this study, spatial transcriptomics and metabolomics were used to analyze APAs, revealing intratumoral transcriptional heterogeneity and identifying transcriptional markers for different biological pathways. The study also found transcriptomic differences between APA-KCNJ5(MUT) and APA-KCNJ5(WT), as well as a correlation between the accumulation of oxidative stress-promoting metabolites and cell death in APA-KCNJ5(WT) and the abundance of antioxidant metabolites in APA-KCNJ5(MUT) . These findings provide insights into the pathogenesis of APA and its genotype-dependent capacities for tumor expansion.
Review
Endocrinology & Metabolism
Cristian A. Carvajal, Alejandra Tapia-Castillo, Andrea Vecchiola, Rene Baudrand, Carlos E. Fardella
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2020)
Article
Endocrinology & Metabolism
Eric R. Barros, Juan Pablo Rigalli, Alejandra Tapia-Castillo, Andrea Vecchiola, Morag J. Young, Joost G. J. Hoenderop, Rene J. M. Bindels, Carlos E. Fardella, Cristian A. Carvajal
Summary: This study evaluated the proteome of urinary extracellular vesicles (uEVs) from patients with primary aldosteronism (PA) and identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, suggesting AGP1 as a potential biomarker for PA. Additionally, the concentration of uEVs was positively correlated with urinary creatinine, and the size of uEVs in PA patients was smaller compared to the control group, indicating differences in uEV characteristics between the two groups.
Article
Biochemistry & Molecular Biology
Eric R. Barros Lamus, Valentina Carotti, Christine R. S. de Vries, Femke Witsel, Onno J. Arntz, Fons A. J. van de Loo, Cristian A. Carvajal, Rene J. M. Bindels, Joost G. J. Hoenderop, Juan P. Rigalli
Summary: This study investigates the regulatory effect of EVs from renal proximal tubule and collecting duct cells on extracellular ATP levels and the expression of the alpha subunit of the epithelial sodium channel. The findings reveal that EVs can modulate purinergic signaling through mechanisms such as miRNA regulation and ATPase activity, impacting renal physiological and pathophysiological processes. Further research on EV release and cargo content may shed light on the role of EVs in renal purinergic signaling.
Article
Urology & Nephrology
Charles J. Blijdorp, Omar A. Z. Tutakhel, Thomas A. Hartjes, Thierry P. P. van den Bosch, Martijn H. van Heugten, Juan Pablo Rigalli, Rob Willemsen, Usha M. Musterd-Bhaggoe, Eric R. Barros, Roger Carles-Fontana, Cristian A. Carvajal, Onno J. Arntz, Fons A. J. van de Loo, Guido Jenster, Marian C. Clahsen-van Groningen, Cathy A. Cuevas, David Severs, Robert A. Fenton, Martin E. van Royen, Joost G. J. Hoenderop, Rene J. M. Bindels, Ewout J. Hoorn
Summary: This study investigated the quantification and characterization of urinary extracellular vesicles (uEVs) in spot urines from healthy individuals and patients with kidney disease. The research found a strong correlation between urine particle and creatinine concentrations, as well as effects of water loading on uEV size and protein detection. Additionally, using detergent improved intracellular-epitope recognition in uEVs and suggested specific binding of exosome markers CD9 and CD63 with distal nephron markers.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Peripheral Vascular Disease
Andrea Vecchiola, Killen Garcia, Luis M. Gonzalez-Gomez, Alejandra Tapia-Castillo, Rocio Artigas, Rene Baudrand, Alexis M. Kalergis, Cristian A. Carvajal, Carlos E. Fardella
Summary: The study showed that PAI-1 and adiponectin have the strongest associations with MetS components, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses are needed to determine if these adipocytokines can predict the progression of MetS and cardiovascular risk.
AMERICAN JOURNAL OF HYPERTENSION
(2022)
Article
Multidisciplinary Sciences
Alejandra Tapia-Castillo, Cristian A. Carvajal, Xaviera Lopez-Cortes, Andrea Vecchiola, Carlos E. Fardella
Summary: Nonclassic apparent mineralocorticoid excess (NC-AME) is a novel clinical condition characterized by higher blood pressure and altered metabolism compared to healthy controls. Metabolomic analyses identified potential biomarkers and differential metabolites between NC-AME and control subjects, suggesting a distinct metabolic profile associated with this condition. Further studies are needed to elucidate the biological role of these metabolites in NC-AME.
SCIENTIFIC REPORTS
(2021)
Review
Endocrinology & Metabolism
Cristian A. Carvajal, Alejandra Tapia-Castillo, Jorge A. Perez, Carlos E. Fardella
Summary: Primary aldosteronism is an endocrine related condition that causes arterial hypertension due to inappropriately high and unregulated aldosterone concentration. Recent studies have recognized a broad spectrum of this condition, posing new challenges in early identification. Extracellular vesicles (EVs) and their cargo have shown potential as novel biomarkers for diagnosing and predicting outcomes in primary aldosteronism.
Article
Immunology
Cristian A. Carvajal, Alejandra Tapia-Castillo, Jorge A. Perez, Carlos E. Fardella
Summary: Primary aldosteronism (PA) is a common cause of secondary hypertension with a prevalence of 6-10%. This cross-sectional study found that PA patients had significantly higher blood pressure, increased AGP1 protein in serum, and decreased miR-21-5p in uEVs, suggesting AGP1 and uEV-miR-21-5p could be potential biomarkers for PA.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yi-Zhou Yao, Francine E. Brennan, Cristian A. Carvajal, Andrea Vecchiola, Alejandra Tapia-Castillo, Carlos E. Fardella, Peter J. Fuller
Summary: Cortisol resistance has been observed in degus, a type of New World hystricomorph endemic to central Chile. Degus are commonly used in studies related to stress, diurnal rhythms, parental behavior, and female masculinization. Similar to the guinea pig, another type of New World hystricomorph, degus also exhibit glucocorticoid resistance due to different amino acid sequences in their glucocorticoid receptors (GR). However, the specific amino acids and regions responsible for resistance in guinea pig GR are not applicable to degu GR. Instead, the resistance to cortisol in degu GR is caused by the substitution of two isoleucine residues with a valine doublet in the region between helices 5 and 6 of the GR ligand-binding domain (LBD).
Article
Endocrinology & Metabolism
Alejandra Tapia-Castillo, Cristian A. Carvajal, Jorge A. Perez, Carlos E. Fardella
Summary: This study identified adult subjects with a combined condition of nonclassic apparent mineralocorticoid excess (NCAME) and primary aldosteronism (PA), who had higher blood pressure and increased markers of renal and endothelial damage. Additionally, certain miRNA expressions were associated with this novel combined phenotype.
Article
Endocrinology & Metabolism
Valentina Pasten, Alejandra Tapia-Castillo, Carlos E. Fardella, Andrea Leiva, Cristian A. Carvajal
Summary: This study found that 18% of normotensive pregnant women had either high aldosterone or high renin levels, suggesting a subclinical status similar to primary aldosteronism or hyperreninemia, respectively. sEVs and their specific cargo should be further studied to clarify their role as potential biomarkers of RAAS alterations in pregnant women.
Article
Medicine, General & Internal
Andrea Vecchiola, Cristobal A. Fuentes, Cristian A. Carvajal, Carmen Campino, Fidel Allende, Alejandra Tapia-Castillo, Carlos F. Lagos, Carlos E. Fardella
Summary: The study revealed that testosterone inhibits the enzymes associated with Familial hyperaldosteronism type I, showing higher efficacy and potency on ASWT compared to ASCE. Molecular modelling studies demonstrated different orientations of testosterone in the crystal structures of ASWT and ASCE.
REVISTA MEDICA DE CHILE
(2021)
Letter
Endocrinology & Metabolism
Cristian A. Carvajal, Alejandra Tapia-Castillo, Carlos E. Fardella
Correction
Endocrinology & Metabolism
C. A. Carvajal, A. Tapia-Castillo, A. Vecchiola, R. Baudrand, C. E. Fardella
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Eugenio Arteaga, Felipe Valenzuela, Carlos F. Lagos, Marcela Lagos, Alejandra Martinez, Rene Baudrand, Cristian Carvajal, Carlos E. Fardella
