دورية أكاديمية
Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.
| العنوان: | Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques. |
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| المؤلفون: | Diez Benavente E; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Karnewar S; Robert M. Berne Cardiovascular Research Center (S.K., G.K.O.), University of Virginia, Charlottesville., Buono M; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Mili E; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Hartman RJG; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Kapteijn D; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Slenders L; Central Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Daniels M; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Aherrahrou R; Center for Public Health Genomics (R.A., M.C.), University of Virginia, Charlottesville.; Institute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.).; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland (R.A.)., Reinberger T; Institute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.)., Mol BM; Department of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands., de Borst GJ; Department of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands., de Kleijn DPV; Department of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Prange KHM; Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam University Medical Centers - location AMC, University of Amsterdam, Netherlands (K.H.M.P., M.P.J.d.W.)., Depuydt MAC; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.A.C.D., J.K.)., de Winther MPJ; Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam University Medical Centers - location AMC, University of Amsterdam, Netherlands (K.H.M.P., M.P.J.d.W.)., Kuiper J; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.A.C.D., J.K.)., Björkegren JLM; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York (J.L.M.B.).; Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden (J.L.M.B.)., Erdmann J; Institute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.)., Civelek M; Center for Public Health Genomics (R.A., M.C.), University of Virginia, Charlottesville.; Department of Biomedical Engineering (M.C.).; University of Virginia, Charlottesville (M.C.)., Mokry M; Central Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands., Owens GK; Robert M. Berne Cardiovascular Research Center (S.K., G.K.O.), University of Virginia, Charlottesville., Pasterkamp G; Central Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands., den Ruijter HM; Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands. |
| المصدر: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2023 Oct; Vol. 43 (10), pp. 1836-1850. Date of Electronic Publication: 2023 Aug 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas, TX : American Heart Association, c1995- |
| مواضيع طبية MeSH: | Plaque, Atherosclerotic*/pathology , Coronary Artery Disease*/pathology , Atherosclerosis*/pathology, Female ; Male ; Humans ; Mice ; Animals ; Gene Regulatory Networks ; Myofibroblasts/metabolism ; Myocytes, Smooth Muscle/metabolism |
| مستخلص: | Background: Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. Methods: Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male Apoe -/- mice fed a Western diet for 18 and 30 weeks. Results: Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene MFGE8 (milk fat globule EGF and factor V/VIII domain containing) showed retained expression in advanced plaques from female mice but was downregulated in male mice during atherosclerosis progression. Conclusions: Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs. Competing Interests: Disclosures None. |
| التعليقات: | Update of: bioRxiv. 2023 Feb 09;:. (PMID: 36798294) |
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| معلومات مُعتمدة: | R01 HL136314 United States HL NHLBI NIH HHS; R01 HL141425 United States HL NHLBI NIH HHS; R01 HL156849 United States HL NHLBI NIH HHS; R01 HL166161 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: coronary artery disease; gene expression; lipids; plaque; women's health |
| تواريخ الأحداث: | Date Created: 20230817 Date Completed: 20231004 Latest Revision: 20240420 |
| رمز التحديث: | 20240420 |
| مُعرف محوري في PubMed: | PMC10521798 |
| DOI: | 10.1161/ATVBAHA.123.319325 |
| PMID: | 37589136 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1524-4636 |
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| DOI: | 10.1161/ATVBAHA.123.319325 |