Page 13 - GTM-4-3

Global Translational Medicine Inflammation in CVD: Mechanisms and markers

Table 1. Pro‑inflammatory markers and their mechanisms in ligand-1 (PSGL-1) on monocytes and neutrophils. This
9
atherosclerotic inflammation interaction facilitates leukocyte rolling, adhesion, and
infiltration into the arterial intima, promoting local
Pro‑inflammatory marker Mechanisms in atherosclerotic
inflammation inflammation, foam cell formation, and plaque progression.
Interleukin (IL)-1α IL-1α functions as an alarmin Sustained P-selectin/PSGL-1 signaling activation amplifies
released upon necrotic cell death. It is cytokine release, fosters platelet–leukocyte aggregation,
constitutively expressed in endothelial and contributes to both microvascular dysfunction and
and epithelial cells. It binds to IL-1 thrombotic instability. Genetic polymorphisms in the SELP
receptor type 1 (IL-1R1) to activate gene have been associated with elevated soluble P-selectin
NF-κB, MAPK, and JNK pathways, levels and increased cardiovascular risk, suggesting a role
promoting early local inflammation, 9
leukocyte recruitment, and induction in inflammatory risk stratification. Furthermore, anti-P-
of IL-1β. It is central to initiating the selectin therapies, such as crizanlizumab and inclaclumab,
IL-1-driven inflammatory loop in have demonstrated early promise in reducing myocardial
ASCVD. injury and dampening inflammatory thrombotic
IL-1β The binding of IL-1β to IL-1R1 activates responses, underscoring the translational potential of this
signal pathways such as NF-κB, JNK, and pathway in ASCVD.
p38 MAPK and induces expressions of
genes such as IL-6, IL-8, MCP-1, COX-2, Meanwhile, GDF15, a member of the transforming
IL-1α, and IL-1β. growth factor-beta superfamily, is a stress-responsive
IL-6 Multi-modal pathways are noted. cytokine upregulated in response to ischemic injury,
IL-6 binds to membrane-bound IL-6 pressure overload, oxidative stress, and systemic
receptors present on hepatocytes, inflammation. It integrates signals from cardiometabolic,
some leukocytes, and endothelial
cells (classic signaling); to soluble inflammatory, and mechanical stress pathways, making it
forms of the IL-6 receptors, which a broad cardiovascular risk marker. Persistently elevated
allow signaling in most other cell GDF15 levels reflect maladaptive remodeling and are
types (trans-signaling); or through independently associated with adverse outcomes in
trans-presentation from dendritic cells coronary artery disease, heart failure, and atrial fibrillation
to T cells (trans-presentation). All
modes of signaling converge on the – even after adjustment for natriuretic peptides and
10
membrane signal-transducing receptor troponins. Its prognostic value across large cohorts has
subunit glycoprotein 130 to activate positioned GDF15 as a promising tool for inflammatory
the intracellular Janus kinase signal risk stratification. In addition, the incorporation of GDF15
transducer and activator of transcription into multi-marker models improves the prediction of
pathway.
Myeloperoxidase (MPO) Released by inflammatory cells, MPO mortality and hospitalization, reinforcing its utility in
identifying patients with high-risk, inflammation-driven
catalyzes oxidative modifications of LDL
and HDL, impairing cholesterol efflux CVD.
and destabilizing plaques.
High-sensitivity C-reactive Synthesized in the liver in response 2.6. The role of adaptive immunity
protein (hs-CRP) to IL-6 activation, hs-CRP serves as a The adaptive immune system plays a pivotal role in the
marker of systemic inflammation and pathogenesis of ASCVD, contributing to the progression
cardiovascular risk. and regulation of atherosclerotic plaques. The key
Lipoprotein-associated Lp-PLA2 is associated with LDL particles. components of this system include antigen-presenting
phospholipase A2 It promotes oxidative stress and releases cells, CD4 T-helper cells, and B lymphocytes, all of which
+
(Lp-PLA2) pro-inflammatory mediators, driving
plaque progression. orchestrate targeted immune responses within the arterial
Trimethylamine-N-oxide Derived from the gut microbiome, wall.
(TMAO) TMAO enhances vascular inflammation Antigen-presenting cells, such as dendritic cells and
by promoting cholesterol deposition and macrophages, process and present oxidized LDL and other
foam cell formation.
atherogenic antigens through major histocompatibility
Abbreviations: ASCVD: Atherosclerotic cardiovascular disease; complex molecules to naive T cells. 11,12 This interaction
COX-2: Cyclo-oxygenase-2; JNK: c-Jun N-terminal kinase; MAPK: +
Mitogen-activated protein kinase; MCP-1: Monocyte chemoattractant drives the differentiation of CD4 T cells into distinct
protein-1; NF-κB: Nuclear factor-kappa B. subsets with varying impacts on atherogenesis. T helper

Volume 4 Issue 3 (2025) 5 doi: 10.36922/GTM025100023