Circulation researchPub Date : 2024-12-06Epub Date: 2024-12-05DOI: 10.1161/RES.0000000000000702
{"title":"Correction to: Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF.","authors":"","doi":"10.1161/RES.0000000000000702","DOIUrl":"https://doi.org/10.1161/RES.0000000000000702","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"135 12","pages":"e154"},"PeriodicalIF":16.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Circulation researchPub Date : 2024-12-06Epub Date: 2024-12-05DOI: 10.1161/CIRCRESAHA.124.325719
Selam Desta, Claude F Albritton, Annet Kirabo
{"title":"Salt's Sex-Specific Impact of Gut Microbiota in Hypertension.","authors":"Selam Desta, Claude F Albritton, Annet Kirabo","doi":"10.1161/CIRCRESAHA.124.325719","DOIUrl":"10.1161/CIRCRESAHA.124.325719","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"135 12","pages":"1138-1140"},"PeriodicalIF":16.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Circulation researchPub Date : 2024-11-08Epub Date: 2024-10-01DOI: 10.1161/CIRCRESAHA.124.324938
Pegah Ramezani Rad, Vanasa Nageswaran, Lisa Peters, Leander Reinshagen, Johann Roessler, Szandor Simmons, Erik Asmus, Corey Wittig, Markus C Brack, Geraldine Nouailles, Emiel P C van der Vorst, Sanne L Maas, Kristina Sonnenschein, Barbara J H Verhaar, Robert Szulcek, Martin Witzenrath, Ulf Landmesser, Wolfgang M Kuebler, Arash Haghikia
{"title":"Pneumonia Induced Rise in Glucagon Promotes Endothelial Damage and Thrombogenicity.","authors":"Pegah Ramezani Rad, Vanasa Nageswaran, Lisa Peters, Leander Reinshagen, Johann Roessler, Szandor Simmons, Erik Asmus, Corey Wittig, Markus C Brack, Geraldine Nouailles, Emiel P C van der Vorst, Sanne L Maas, Kristina Sonnenschein, Barbara J H Verhaar, Robert Szulcek, Martin Witzenrath, Ulf Landmesser, Wolfgang M Kuebler, Arash Haghikia","doi":"10.1161/CIRCRESAHA.124.324938","DOIUrl":"10.1161/CIRCRESAHA.124.324938","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1116-1118"},"PeriodicalIF":16.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>LRP1</i> Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases.","authors":"Lu Liu, Joséphine Henry, Yingwei Liu, Charlène Jouve, Jean-Sébastien Hulot, Adrien Georges, Nabila Bouatia-Naji","doi":"10.1161/CIRCRESAHA.124.325269","DOIUrl":"10.1161/CIRCRESAHA.124.325269","url":null,"abstract":"<p><strong>Background: </strong>Genome-wide association studies implicate common genetic variations in the <i>LRP1</i> (low-density lipoprotein receptor-related protein 1 gene) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown.</p><p><strong>Methods: </strong>Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells were genome-edited using CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein 9) to delete or modify candidate enhancer regions and generate <i>LRP1</i> knockout cell lines. Cells were differentiated into smooth muscle cells through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown, and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA sequencing, and mass spectrometry.</p><p><strong>Results: </strong>Multitrait colocalization analyses pointed at rs11172113 as the most likely causal variant in <i>LRP1</i> for fibromuscular dysplasia, migraine, pulse pressure, and spontaneous coronary artery dissection. We found the rs11172113-T allele to associate with higher <i>LRP1</i> expression. Genomic deletion in induced pluripotent stem cell-derived smooth muscle cells supported rs11172113 to locate in an enhancer region regulating <i>LRP1</i> expression. We found transcription factors MECP2 (methyl CpG binding protein 2) and SNAIL (Zinc Finger Protein SNAI1) to repress <i>LRP1</i> expression through an allele-specific mechanism, involving SNAIL interaction with disease risk allele. <i>LRP1</i> knockout decreased induced pluripotent stem cell-derived smooth muscle cell proliferation and migration. Differentially expressed genes were enriched for collagen-containing extracellular matrix and connective tissue development. <i>LRP1</i> knockout and deletion of rs11172113 enhancer showed potentiated canonical TGF-β (transforming growth factor beta) signaling through enhanced phosphorylation of SMAD2/3 (Mothers against decapentaplegic homolog 2/3). Analyses of the protein content of decellularized extracts indicated partial extracellular matrix remodeling involving enhanced secretion of CYR61 (cystein rich angiogenic protein 61), a known LRP1 ligand involved in vascular integrity and TIMP3 (Metalloproteinase inhibitor 3), implicated in extracellular matrix maintenance and also known to interact with LRP1.</p><p><strong>Conclusions: </strong>Our findings support allele-specific <i>LRP1</i> expression repression by the endothelial-to-mesenchymal transition regulator SNAIL. We propose decreased <i>LRP1</i> expression in smooth muscle cells to remodel the extracellular matrix enhanced by TGF-β as a potential mechanism of this pleiotropic locus for vascular diseases.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1084-1097"},"PeriodicalIF":16.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Circulation researchPub Date : 2024-11-08Epub Date: 2024-11-07DOI: 10.1161/RES.0000000000000700
{"title":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000700","DOIUrl":"https://doi.org/10.1161/RES.0000000000000700","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"135 11","pages":"1030-1032"},"PeriodicalIF":16.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Circulation researchPub Date : 2024-10-25Epub Date: 2024-10-01DOI: 10.1161/CIRCRESAHA.124.325305
Manako Yamaguchi, Lucas Ferreira de Almeida, Hiroki Yamaguchi, Xiuyin Liang, Jason P Smith, Silvia Medrano, Maria Luisa S Sequeira-Lopez, R Ariel Gomez
{"title":"Transformation of the Kidney into a Pathological Neuro-Immune-Endocrine Organ.","authors":"Manako Yamaguchi, Lucas Ferreira de Almeida, Hiroki Yamaguchi, Xiuyin Liang, Jason P Smith, Silvia Medrano, Maria Luisa S Sequeira-Lopez, R Ariel Gomez","doi":"10.1161/CIRCRESAHA.124.325305","DOIUrl":"10.1161/CIRCRESAHA.124.325305","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1025-1027"},"PeriodicalIF":16.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pritam Bardhan,Xue Mei,Ngoc Khanh Lai,Blair Mell,Ramakumar Tummala,Sachin Aryal,Ishan Manandhar,Hyeongu Hwang,Tania Akter Jhuma,Rohit R Atluri,Jun Kyoung,Ying Li,Bina Joe,Hong-Bao Li,Tao Yang
{"title":"Salt Responsive Gut Microbiota Induces Sex Specific Blood Pressure Changes.","authors":"Pritam Bardhan,Xue Mei,Ngoc Khanh Lai,Blair Mell,Ramakumar Tummala,Sachin Aryal,Ishan Manandhar,Hyeongu Hwang,Tania Akter Jhuma,Rohit R Atluri,Jun Kyoung,Ying Li,Bina Joe,Hong-Bao Li,Tao Yang","doi":"10.1161/circresaha.124.325056","DOIUrl":"https://doi.org/10.1161/circresaha.124.325056","url":null,"abstract":"BACKGROUNDTryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota. The gut microbiota has been recognized as a regulator of blood pressure. Furthermore, there is ample evidence for sex differences in the gut microbiota. However, it is unclear whether such sex differences impact blood pressure differentially through the tryptophan-indole pathway.METHODSTo study the sex-specific mechanisms of gut microbiota-mediated tryptophan-indole pathway in hypertension, we generated a novel rat model with Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9)-targeted deletion of Ace2 in the Dahl salt-sensitive rat. Cecal microbiota transfers from donors of both sexes to female S recipients were performed. Also, Dahl salt-sensitive rats of both sexes were orally gavaged with indole to investigate blood pressure response.RESULTSThe female gut microbiota and its tryptophan-indole pathway exhibited greater buffering capacity when exposed to tryptophan, due to Ace2 deficiency, and salt. In contrast, the male gut microbiota and its tryptophan-indole pathway were more vulnerable. Female rats with male cecal microbiota responded to salt with a higher blood pressure increase. Indole, a tryptophan-derived metabolite produced by gut bacteria, increased blood pressure in male but not in female rats. Moreover, salt altered host-mediated tryptophan metabolism, characterized by reduced serum serotonin of both sexes and higher levels of kynurenine derivatives in the females.CONCLUSIONSWe uncovered a novel sex-specific mechanism in the gut microbiota-mediated tryptophan-indole pathway in blood pressure regulation. Salt tipped the tryptophan metabolism between the host and gut microbiota in a sex-dependent manner. Our study provides evidence for a novel concept that gut microbiota and its metabolism play sex-specific roles in the development of salt-sensitive hypertension.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"32 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}