Jinglian Yan PhD, Guodong Tie PhD, Amanda Tutto MS, Louis M. Messina MD
{"title":"Hypercholesterolemia impairs collateral artery enlargement by ten-eleven translocation 1-dependent hematopoietic stem cell autonomous mechanism in a murine model of limb ischemia","authors":"Jinglian Yan PhD, Guodong Tie PhD, Amanda Tutto MS, Louis M. Messina MD","doi":"10.1016/j.jvssci.2024.100203","DOIUrl":"10.1016/j.jvssci.2024.100203","url":null,"abstract":"<div><h3>Objective</h3><p>The extent of collateral artery enlargement determines the risk of limb loss due to peripheral arterial disease. Hypercholesterolemia impairs collateral artery enlargement, but the underlying mechanism remains poorly characterized. This study tests the hypothesis that hypercholesterolemia impairs collateral artery enlargement through a ten-eleven translocation 1 (Tet1)-dependent hematopoietic stem cell (HSC)-autonomous mechanism that increases their differentiation into proinflammatory Ly6C<sup>hi</sup> monocytes and restricts their conversion into proangiogenic Ly6C<sup>low</sup> monocytes.</p></div><div><h3>Methods</h3><p>To test our hypothesis, we induced limb ischemia and generated chimeric mouse models by transplanting HSCs from either wild-type (WT) mice or hypercholesterolemic mice into lethally irradiated WT recipient mice.</p></div><div><h3>Results</h3><p>We found that the lethally irradiated WT recipient mice reconstituted with HSCs from hypercholesterolemic mice displayed lower blood flow recovery and collateral artery enlargement that was nearly identical to that observed in hypercholesterolemic mice, despite the absence of hypercholesterolemia and consistent with an HSC-autonomous mechanism. We showed that hypercholesterolemia impairs collateral artery enlargement by a Tet1-dependent mechanism that increases HSC differentiation toward proinflammatory Ly6C<sup>hi</sup> monocytes and restricts the conversion of Ly6C<sup>hi</sup> monocytes into proangiogenic Ly6C<sup>low</sup> monocytes. Moreover, Tet1 epigenetically reprograms monocyte gene expression within the HSCs. Restoration of Tet1 expression in HSCs of hypercholesterolemic mice restores WT collateral artery enlargement and blood flow recovery after induction of hindlimb ischemia.</p></div><div><h3>Conclusions</h3><p>These results show that hypercholesterolemia impairs collateral artery enlargement by a novel Tet1-dependent HSC-autonomous mechanism that epigenetically reprograms monocyte gene expression within the HSCs.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100203"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000142/pdfft?md5=49f36588f10b5565ecc9178f0c001b46&pid=1-s2.0-S2666350324000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Calvin Chao MD , Caitlyn Dang BS , Nidhi Reddy BA , Sara Alharbi MS , Jimmy Doan , Akashraj Karthikeyan , Brandon Applewhite PhD , Bin Jiang PhD
{"title":"Characterization of a phenol-based model for denervation of the abdominal aorta and its implications for aortic remodeling","authors":"Calvin Chao MD , Caitlyn Dang BS , Nidhi Reddy BA , Sara Alharbi MS , Jimmy Doan , Akashraj Karthikeyan , Brandon Applewhite PhD , Bin Jiang PhD","doi":"10.1016/j.jvssci.2024.100202","DOIUrl":"10.1016/j.jvssci.2024.100202","url":null,"abstract":"<div><h3>Objective</h3><p>Sympathetic innervation plays a pivotal role in regulating cardiovascular health, and its dysregulation is implicated in a wide spectrum of cardiovascular diseases. This study seeks to evaluate the impact of denervation of the abdominal aorta on its morphology and wall homeostasis.</p></div><div><h3>Methods</h3><p>Male and female Sprague-Dawley rats (N = 12), aged 3 months, underwent midline laparotomy for infrarenal aorta exposure. Chemical denervation was induced via a one-time topical application of 10% phenol (n = 6), whereas sham controls received phosphate-buffered saline (n = 6). Animals were allowed to recover and subsequently were sacrificed after 6 months for analysis encompassing morphology, histology, and immunohistochemistry.</p></div><div><h3>Results</h3><p>At 6 months post-treatment, abdominal aortas subjected to phenol denervation still exhibited a significant reduction in nerve fiber density compared with sham controls. Denervated aortas demonstrated reduced intima-media thickness, increased elastin fragmentation, decreased expression of vascular smooth muscle proteins (α-SMA and MYH11), and elevated adventitial vascular density. Sex-stratified analyses revealed additional dimorphic responses, particularly in aortic collagen and medial cellular density in female animals.</p></div><div><h3>Conclusions</h3><p>Single-timepoint phenol-based chemical denervation induces alterations in abdominal aortic morphology and vascular remodeling over a 6-month period. These findings underscore the potential of the sympathetic nervous system as a therapeutic target for aortic pathologies.</p></div><div><h3>Clinical Relevance</h3><p>Aortic remodeling remains an important consideration in the pathogenesis of aortic disease, including occlusive, aneurysmal, and dissection disease states. The paucity of medical therapies for the treatment of aortic disease has driven considerable interest in elucidating the pathogenesis of these conditions; new therapeutic targets are critically needed. Here, we show significant remodeling after phenol-induced denervation with morphologic, histologic, and immunohistochemical features. Future investigations should integrate sympathetic dysfunction as a potential driver of pathologic aortic wall changes with additional consideration of the sympathetic nervous system as a therapeutic target.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000130/pdfft?md5=a268668ec326d9c73541b8e91aa1791d&pid=1-s2.0-S2666350324000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140401435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuai Yuan, Yuhao Sun, Jie Chen, Pranav Sharma, Michael G. Levin, Susanna Larsson, Scott M. Damrauer
{"title":"Associations of Genetic and Lifestyle Risk Factors With Incident Peripheral Artery Disease: A Prospective Cohort Study","authors":"Shuai Yuan, Yuhao Sun, Jie Chen, Pranav Sharma, Michael G. Levin, Susanna Larsson, Scott M. Damrauer","doi":"10.1016/j.jvssci.2024.100258","DOIUrl":"10.1016/j.jvssci.2024.100258","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100258"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steven R. Botts, Kristen Schulz, Corey A. Scipione, Sneha Raju, Leandro C. Breda, Kamalben Prajapati, Kai Yu, Aniqa Khan, Chanele K. Polenz, Sharon J. Hyduk, Joshua D. Wythe, Clint S. Robbins, Myron I. Cybulsky, Jason E. Fish, Kathryn L. Howe
{"title":"Loss of the ETS Transcription Factor ERG Disrupts Fate-defining Programs in the Aortic Endothelium and Promotes Expansion of Endothelial Lineage Cells in Atherosclerotic Plaque","authors":"Steven R. Botts, Kristen Schulz, Corey A. Scipione, Sneha Raju, Leandro C. Breda, Kamalben Prajapati, Kai Yu, Aniqa Khan, Chanele K. Polenz, Sharon J. Hyduk, Joshua D. Wythe, Clint S. Robbins, Myron I. Cybulsky, Jason E. Fish, Kathryn L. Howe","doi":"10.1016/j.jvssci.2024.100239","DOIUrl":"10.1016/j.jvssci.2024.100239","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100239"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brandon T. Gaston, Varun Singh, Anil Kharga, Kevin Deng, Kang Mi Lee, Marc Succi, Anahita Dua, James F. Markmann
{"title":"Development of a Bio-Hybrid Endovascular Stent-Graft That Enables Immunosuppression Free Islet Cell Transplantation","authors":"Brandon T. Gaston, Varun Singh, Anil Kharga, Kevin Deng, Kang Mi Lee, Marc Succi, Anahita Dua, James F. Markmann","doi":"10.1016/j.jvssci.2024.100264","DOIUrl":"10.1016/j.jvssci.2024.100264","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100264"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian Barksdale, Jonah Silverman, Ethan Fannin, Ryan Gedney, Victoria Mattia, Mario Figueroa, Ying Xiong, Rupak Mukherjee, Jeffrey A. Jones, Jean Marie Ruddy
{"title":"Biomechanical Forces Can Promote SGK-1-dependent Expression of Pathologic Matrix Markers","authors":"Christian Barksdale, Jonah Silverman, Ethan Fannin, Ryan Gedney, Victoria Mattia, Mario Figueroa, Ying Xiong, Rupak Mukherjee, Jeffrey A. Jones, Jean Marie Ruddy","doi":"10.1016/j.jvssci.2024.100255","DOIUrl":"10.1016/j.jvssci.2024.100255","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100255"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gloriani Sanchez, Fujie Zhao, Levi Wood, Luke P. Brewster
{"title":"Piezo-1 Expression Decreases Under Disturbed Flow Model of Femoral Atherosclerosis","authors":"Gloriani Sanchez, Fujie Zhao, Levi Wood, Luke P. Brewster","doi":"10.1016/j.jvssci.2024.100261","DOIUrl":"10.1016/j.jvssci.2024.100261","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100261"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}