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Unruly Natural Killer Cells May Figure in
CVD Risk in HIV+ Adolescents
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AIDS 2024, July 22-26, 2024, Munich
Mark Mascolini
Higher cardiovascular disease (CVD) risk in adolescents with perinatally acquired HIV than in matched adolescents never exposed to HIV may be traced in part to higher activation, maturation, and other traits of natural killer (NK) cells in the HIV group [1]. This 38-person cross-sectional comparison of Ugandan adolescents with HIV and matched HIV-unexposed youngsters found significant correlations between abnormal NK cell subsets and carotid intima media thickness (CIMT) as well as pulse wave velocity (PWV)-early signals of higher atherosclerotic risk.
Research has established higher CVD rates in 18- to 34-year-olds with HIV than in age-matched HIV-negative controls [2]. As more children with perinatally acquired HIV survive into adolescence and adulthood, observed Namal Livange and colleagues from Ohio State University, CVD risk outpaces that in HIV-negative people the same age. Researchers have advanced several theories to explain this CVD difference, but no one has looked closely at a potential role for NK cells
Livange and workers set out to do just that in children taking antiretroviral therapy (ART) for at least 2 years, including the last 6 months with a viral load below 400 copies while taking the same regimen. They matched these perinatally infected children by age and sex to control children never exposed to HIV.
This preliminary cross-sectional analysis involved 18 youngsters with HIV and 20 without HIV who gave samples of whole blood and peripheral blood mononuclear cells. Imaging to assess CVD risk included CIMT and PWV, a measure of arterial stiffness. CIMT proved greater (worse) in the HIV group (+0.0183 mm IMT max), as did PWV (+0.2794 m/sec).
The Ohio State team also found differentially expressed genes linked to immune activation, immune cell migration to inflamed tissue, vascular wall remodeling, oxidized low-density lipoprotein (Ox-LDL) uptake, and histone modification and DNA methylation in the group with HIV. In a gene ontology analysis, the researchers uncovered evidence of increased inflammatory response to antigenic stimuli, chronic inflammatory response, positive regulation of NK cell activation, regulation of lipid storage, and other CVD-related variables.
Ox-LDL, linked to CVD by a vicious cycle of atherosclerosis and inflammation, is usually significantly increased in people with CVD but in this study was significantly lower in the adolescent HIV group. However, the study disclosed strong correlations between plasma Ox-LDL and NK cell subsets in adolescents with HIV.
Cluster mapping showed persistent alterations in monocytes and NK cells of perinatally infected children. The researchers found higher levels of memory-like proinflammatory NK cell subsets in the adolescents with HIV.
The Ohio State team proposed that "NK cells play a major role in 'atherogenesis' in perinatally acquired HIV infection." Activated NK cells boosted Ox-LDL uptake by monocyte-derived macrophages, possibly via the NKG2D receptor. For the first time, they said, their data "reveal an increase in several activated, mature NK subsets capable of homing to vascular tissue."
The researchers suggested their findings could point to new prevention and treatment tactics to lower risk of early CVD in young people with perinatally acquired HIV. They plan ongoing follow-up of these adolescents to monitor cardiometabolic markers and to learn whether their immunophenotypes correlate with other non-AIDS comorbidities.
Increased cardiovascular risk in perinatally HIV-acquired adolescents (PHIV) may linked to proinflammatory NK cells - (07/31/24)....
" the dysregulated NK subsets showed significant correlations with carotid intima-media thickness and pulse wave velocity (PVW)......Dysregulated NK subsets exhibit significant correlations with carotid intima-media thickness and PVW, suggesting a potential link between NK cells and cardiovascular risk in adolescents with PHIV."
References
1. Livange N, Alles MA, Gunasena M, et al. Increased cardiovascular risk in perinatally HIV-acquired adolescents (PHIV) may linked to proinflammatory NK cells. AIDS 2024, July 22-26, 2024, Munich. Abstract OAA0603.
2. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92:2506-12. doi: 10.1210/jc.2006-2190. https://academic.oup.com/jcem/article/92/7/2506/2598256
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