Sex Differences in Circulating Progenitor Cells
BackgroundLower levels of circulating progenitor cells (PCs) reflect impaired endogenous regenerative capacity and are associated with aging, vascular disease, and poor outcomes. Whether biologic sex and sex hormones influence PC numbers remains a subject of controversy. We sought to determine sex d...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.006245 |
| _version_ | 1811332630990290944 |
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| author | Matthew L. Topel Salim S. Hayek Yi‐An Ko Pratik B. Sandesara Ayman Samman Tahhan Iraj Hesaroieh Ernestine Mahar Greg S. Martin Edmund K. Waller Arshed A. Quyyumi |
| author_facet | Matthew L. Topel Salim S. Hayek Yi‐An Ko Pratik B. Sandesara Ayman Samman Tahhan Iraj Hesaroieh Ernestine Mahar Greg S. Martin Edmund K. Waller Arshed A. Quyyumi |
| author_sort | Matthew L. Topel |
| collection | DOAJ |
| description | BackgroundLower levels of circulating progenitor cells (PCs) reflect impaired endogenous regenerative capacity and are associated with aging, vascular disease, and poor outcomes. Whether biologic sex and sex hormones influence PC numbers remains a subject of controversy. We sought to determine sex differences in circulating PCs in both healthy persons and patients with coronary artery disease, and to determine their association with sex hormone levels. Methods and ResultsIn 642 participants (mean age 48 years, 69% women, 23% black) free from cardiovascular disease, we measured circulating PC counts as CD45med+ mononuclear cells coexpressing CD34 and its subsets expressing CD133, chemokine (C‐X‐C motif) receptor 4, and vascular endothelial growth factor receptor 2 epitopes using flow cytometry. Testosterone and estradiol levels were measured. After adjustment for age, cardiovascular risk factors, and body mass, CD34+ (β=−23%, P<0.001), CD34+/CD133+ (β=−20%, P=0.001), CD34+/chemokine (C‐X‐C motif) receptor 4–positive (β=−24%, P<0.001), and CD34+/chemokine (C‐X‐C motif) receptor 4–positive/CD133+ (β=−21%, P=0.001) PC counts, but not vascular endothelial growth factor receptor 2‐positive PC counts were lower in women compared with men. Estradiol levels positively correlated with hematopoietic, but not vascular endothelial growth factor receptor 2‐ positive PC counts in women (P<0.05). Testosterone levels and PC counts were not correlated in men. These findings were replicated in an independent cohort with prevalent coronary artery disease. ConclusionsWomen have lower circulating hematopoietic PC levels compared with men. Estrogen levels are modestly associated with PC levels in women. Since PCs are reflective of endogenous regenerative capacity, these findings may at least partly explain the rise in adverse cardiovascular events in women with aging and menopause. |
| first_indexed | 2024-04-13T16:39:51Z |
| format | Article |
| id | doaj.art-46f4d32505684a94b70bbe5ca914c4d5 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T16:39:51Z |
| publishDate | 2017-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-46f4d32505684a94b70bbe5ca914c4d52022-12-22T02:39:16ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-10-0161010.1161/JAHA.117.006245Sex Differences in Circulating Progenitor CellsMatthew L. Topel0Salim S. Hayek1Yi‐An Ko2Pratik B. Sandesara3Ayman Samman Tahhan4Iraj Hesaroieh5Ernestine Mahar6Greg S. Martin7Edmund K. Waller8Arshed A. Quyyumi9Division of Cardiology, Emory University School of Medicine, Atlanta, GADivision of Cardiology, Emory University School of Medicine, Atlanta, GADepartment of Biostatistics and Bioinformatics, Emory University, Atlanta, GADivision of Cardiology, Emory University School of Medicine, Atlanta, GADivision of Cardiology, Emory University School of Medicine, Atlanta, GADepartment of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GADepartment of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GADepartment of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GADepartment of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GADivision of Cardiology, Emory University School of Medicine, Atlanta, GABackgroundLower levels of circulating progenitor cells (PCs) reflect impaired endogenous regenerative capacity and are associated with aging, vascular disease, and poor outcomes. Whether biologic sex and sex hormones influence PC numbers remains a subject of controversy. We sought to determine sex differences in circulating PCs in both healthy persons and patients with coronary artery disease, and to determine their association with sex hormone levels. Methods and ResultsIn 642 participants (mean age 48 years, 69% women, 23% black) free from cardiovascular disease, we measured circulating PC counts as CD45med+ mononuclear cells coexpressing CD34 and its subsets expressing CD133, chemokine (C‐X‐C motif) receptor 4, and vascular endothelial growth factor receptor 2 epitopes using flow cytometry. Testosterone and estradiol levels were measured. After adjustment for age, cardiovascular risk factors, and body mass, CD34+ (β=−23%, P<0.001), CD34+/CD133+ (β=−20%, P=0.001), CD34+/chemokine (C‐X‐C motif) receptor 4–positive (β=−24%, P<0.001), and CD34+/chemokine (C‐X‐C motif) receptor 4–positive/CD133+ (β=−21%, P=0.001) PC counts, but not vascular endothelial growth factor receptor 2‐positive PC counts were lower in women compared with men. Estradiol levels positively correlated with hematopoietic, but not vascular endothelial growth factor receptor 2‐ positive PC counts in women (P<0.05). Testosterone levels and PC counts were not correlated in men. These findings were replicated in an independent cohort with prevalent coronary artery disease. ConclusionsWomen have lower circulating hematopoietic PC levels compared with men. Estrogen levels are modestly associated with PC levels in women. Since PCs are reflective of endogenous regenerative capacity, these findings may at least partly explain the rise in adverse cardiovascular events in women with aging and menopause.https://www.ahajournals.org/doi/10.1161/JAHA.117.006245CD133CD34CXCR4estrogenprogenitor cellvascular endothelial growth factor receptor 2 |
| spellingShingle | Matthew L. Topel Salim S. Hayek Yi‐An Ko Pratik B. Sandesara Ayman Samman Tahhan Iraj Hesaroieh Ernestine Mahar Greg S. Martin Edmund K. Waller Arshed A. Quyyumi Sex Differences in Circulating Progenitor Cells Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease CD133 CD34 CXCR4 estrogen progenitor cell vascular endothelial growth factor receptor 2 |
| title | Sex Differences in Circulating Progenitor Cells |
| title_full | Sex Differences in Circulating Progenitor Cells |
| title_fullStr | Sex Differences in Circulating Progenitor Cells |
| title_full_unstemmed | Sex Differences in Circulating Progenitor Cells |
| title_short | Sex Differences in Circulating Progenitor Cells |
| title_sort | sex differences in circulating progenitor cells |
| topic | CD133 CD34 CXCR4 estrogen progenitor cell vascular endothelial growth factor receptor 2 |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.006245 |
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