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Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study.
Wednesday,2022-07-20 17:34 America/Los_Angeles — ecterry
| Title | Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Feinstein, MJ, Bůzková, P, Olson, NC, Doyle, MF, Sitlani, CM, Fohner, AE, Huber, SA, Floyd, J, Sinha, A, Thorp, EB, Landay, A, Freiberg, MS, Longstreth, WT, Tracy, RP, Psaty, BM, Delaney, JAc |
| Journal | Atherosclerosis |
| Volume | 351 |
| Pagination | 18-25 |
| Date Published | 2022 06 |
| ISSN | 1879-1484 |
| Keywords | Atherosclerosis, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, Female, Follow-Up Studies, Humans, Incidence, Inflammation, Interleukin-4, Ischemic Stroke, Lymphocyte Activation, Male, Monocytes, Stroke, T-Lymphocyte Subsets |
| Abstract | <p><b>BACKGROUND AND AIMS: </b>Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke.</p><p><b>METHODS: </b>We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models.</p><p><b>RESULTS: </b>We observed associations of intermediate monocytes, early-activated CD4 T cells, and both CD4 and CD8 T cells producing interleukin-4 after cytokine stimulation (T and T, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women.</p><p><b>CONCLUSIONS: </b>Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.</p> |
| DOI | 10.1016/j.atherosclerosis.2022.05.007 |
| Alternate Journal | Atherosclerosis |
| PubMed ID | 35605368 |
| Grant List | R01 HL156792 / HL / NHLBI NIH HHS / United States R01 HL144483 / HL / NHLBI NIH HHS / United States R01 HL120854 / HL / NHLBI NIH HHS / United States HHSN268201500003I / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States UL1 TR001420 / TR / NCATS NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States R01 HL144483 / HL / NHLBI NIH HHS / United States R01 HL120854 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States |
ePub date:
22/06