Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant
Abstract Aims Intercellular adhesion molecule‐1 (ICAM‐1) facilitates inflammation via leucocyte recruitment and has been implicated in heart failure with preserved ejection fraction (HFpEF). Approximately 35% of African American individuals carry a copy of an ICAM1 missense variant (rs5491; p.K56M),...
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Wiley
2024-12-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.14983 |
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| author | Jing Gao Pedro Giro Joseph A. Delaney Laura Rasmussen‐Torvik Kent D. Taylor Edward B. Thorp Margaret F. Doyle Matthew J. Feinstein Colleen M. Sitlani Nels Olson Russell Tracy Sanjiv J. Shah Bruce M. Psaty Ravi B. Patel |
| author_facet | Jing Gao Pedro Giro Joseph A. Delaney Laura Rasmussen‐Torvik Kent D. Taylor Edward B. Thorp Margaret F. Doyle Matthew J. Feinstein Colleen M. Sitlani Nels Olson Russell Tracy Sanjiv J. Shah Bruce M. Psaty Ravi B. Patel |
| author_sort | Jing Gao |
| collection | DOAJ |
| description | Abstract Aims Intercellular adhesion molecule‐1 (ICAM‐1) facilitates inflammation via leucocyte recruitment and has been implicated in heart failure with preserved ejection fraction (HFpEF). Approximately 35% of African American individuals carry a copy of an ICAM1 missense variant (rs5491; p.K56M), which is associated with an increased risk of HFpEF. The pathways by which rs5491 increases HFpEF risk are not well defined. We evaluated the circulating immune cell profile of rs5491. Methods Among African American individuals in the Multi‐Ethnic Study of Atherosclerosis, we evaluated the associations of rs5491 with 29 circulating peripheral blood mononuclear cell subsets. The top immune cells were then related to echocardiographic measures of structure and function. Results Among 502 individuals with immune cell profiling (mean age 63 years, 51% female), 191 individuals (38%) had at least one copy of rs5491. Each additional rs5491 allele was significantly associated with higher proportions of Tc17 CD8+ cytotoxic T cells (β = 1.34, SE = 0.45, P = 9.5 × 10−5) and Tc2 CD8+ cytotoxic T cells (β = 1.19, SE = 0.44, P = 0.00012). There were no other associations noted between rs5491 and the remaining immune cells. A higher proportion of Tc17 cells was significantly associated with a higher left ventricular ejection fraction, E/e′ average and right ventricular systolic pressure (RVSP), while a higher proportion of Tc2 cells was significantly associated with a higher RVSP. Conclusions The ICAM1 p.K56M variant (rs5491) carries a distinct and inflammatory T‐cell subset profile. These cytotoxic T cells are in turn associated with alterations in cardiac function and adverse haemodynamics later in life, thus providing insight into pathways by which rs5491 may increase the risk of HFpEF. |
| format | Article |
| id | doaj-art-9ab7c3c221b44434babc4f74e77fd943 |
| institution | OA Journals |
| issn | 2055-5822 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-9ab7c3c221b44434babc4f74e77fd9432025-08-20T01:54:57ZengWileyESC Heart Failure2055-58222024-12-011164427443110.1002/ehf2.14983Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variantJing Gao0Pedro Giro1Joseph A. Delaney2Laura Rasmussen‐Torvik3Kent D. Taylor4Edward B. Thorp5Margaret F. Doyle6Matthew J. Feinstein7Colleen M. Sitlani8Nels Olson9Russell Tracy10Sanjiv J. Shah11Bruce M. Psaty12Ravi B. Patel13Division of Cardiology Northwestern University Feinberg School of Medicine Chicago Illinois USADivision of Cardiology Northwestern University Feinberg School of Medicine Chicago Illinois USADepartment of Epidemiology University of Washington Seattle Washington USADepartment of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago Illinois USAThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics The Lundquist Institute for Biomedical Innovation at Harbor‐UCLA Medical Center Torrance California USADepartment of Pathology Northwestern University Feinberg School of Medicine Chicago Illinois USADepartment of Pathology and Laboratory Medicine University of Vermont Burlington Vermont USADivision of Cardiology Northwestern University Feinberg School of Medicine Chicago Illinois USACardiovascular Health Research Unit, Department of Medicine University of Washington Seattle Washington USADepartment of Pathology and Laboratory Medicine University of Vermont Burlington Vermont USADepartment of Pathology and Laboratory Medicine University of Vermont Burlington Vermont USADivision of Cardiology Northwestern University Feinberg School of Medicine Chicago Illinois USACardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health University of Washington Seattle Washington USADivision of Cardiology Northwestern University Feinberg School of Medicine Chicago Illinois USAAbstract Aims Intercellular adhesion molecule‐1 (ICAM‐1) facilitates inflammation via leucocyte recruitment and has been implicated in heart failure with preserved ejection fraction (HFpEF). Approximately 35% of African American individuals carry a copy of an ICAM1 missense variant (rs5491; p.K56M), which is associated with an increased risk of HFpEF. The pathways by which rs5491 increases HFpEF risk are not well defined. We evaluated the circulating immune cell profile of rs5491. Methods Among African American individuals in the Multi‐Ethnic Study of Atherosclerosis, we evaluated the associations of rs5491 with 29 circulating peripheral blood mononuclear cell subsets. The top immune cells were then related to echocardiographic measures of structure and function. Results Among 502 individuals with immune cell profiling (mean age 63 years, 51% female), 191 individuals (38%) had at least one copy of rs5491. Each additional rs5491 allele was significantly associated with higher proportions of Tc17 CD8+ cytotoxic T cells (β = 1.34, SE = 0.45, P = 9.5 × 10−5) and Tc2 CD8+ cytotoxic T cells (β = 1.19, SE = 0.44, P = 0.00012). There were no other associations noted between rs5491 and the remaining immune cells. A higher proportion of Tc17 cells was significantly associated with a higher left ventricular ejection fraction, E/e′ average and right ventricular systolic pressure (RVSP), while a higher proportion of Tc2 cells was significantly associated with a higher RVSP. Conclusions The ICAM1 p.K56M variant (rs5491) carries a distinct and inflammatory T‐cell subset profile. These cytotoxic T cells are in turn associated with alterations in cardiac function and adverse haemodynamics later in life, thus providing insight into pathways by which rs5491 may increase the risk of HFpEF.https://doi.org/10.1002/ehf2.14983echocardiographygeneticsheart failure with preserved ejection fractionimmune cellsintercellular adhesion molecule‐1 |
| spellingShingle | Jing Gao Pedro Giro Joseph A. Delaney Laura Rasmussen‐Torvik Kent D. Taylor Edward B. Thorp Margaret F. Doyle Matthew J. Feinstein Colleen M. Sitlani Nels Olson Russell Tracy Sanjiv J. Shah Bruce M. Psaty Ravi B. Patel Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant ESC Heart Failure echocardiography genetics heart failure with preserved ejection fraction immune cells intercellular adhesion molecule‐1 |
| title | Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant |
| title_full | Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant |
| title_fullStr | Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant |
| title_full_unstemmed | Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant |
| title_short | Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant |
| title_sort | immune cell profiling of the icam1 p k56m heart failure with preserved ejection fraction risk variant |
| topic | echocardiography genetics heart failure with preserved ejection fraction immune cells intercellular adhesion molecule‐1 |
| url | https://doi.org/10.1002/ehf2.14983 |
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