Psoriasis and Cardiometabolic Diseases: Shared Genetic and Molecular Pathways

Abstract

A convincing deal of evidence supports the fact that severe psoriasis is associated with cardiovascular diseases. However, the precise underlying mechanisms linking psoriasis and cardiovascular diseases are not well defined. Psoriasis shares common pathophysiologic mechanisms with atherosclerosis and cardiovascular (CV) risk factors. In particular, polymorphism in the IL-23R and IL-23 genes, as well as other genes involved in lipid and fatty-acid metabolism, renin–angiotensin system and endothelial function, have been described in patients with psoriasis and with cardiovascular risk factors. Moreover, systemic inflammation in patients with psoriasis, including elevated serum proinflammatory cytokines (e.g., TNF-α, IL-17, and IL-23) may contribute to an increased risk of atherosclerosis, hypertension, alteration of serum lipid composition, and insulin resistance. The nonlinear and intricate interplay among various factors, impacting the molecular pathways in different cell types, probably contributes to the development of psoriasis and cardiovascular disease (CVD). Future research should, therefore, aim to fully unravel shared and differential molecular pathways underpinning the association between psoriasis and CVD.

Association between the severity of hard-to-treat psoriasis and the prevalence of metabolic syndrome: A hospital-based cross-sectional study in Jakarta, Indonesia

“…The association of MetS and its components (hypertension, abdominal obesity, hyperglycemia, hypertriglyceridemia, and low HDL level) in psoriasis involves genetic factors and overlapping molecular pathways [ 24 ]. In psoriasis, abnormal immune cell activation with upregulation of proinflammatory cytokines led to an immunological cascade, oxidative damage, and collagen accumulation in arteries, which may contribute to blood vessel stiffening and hypertension [ 24 , 25 ]. One of the vasoactive peptides that have a key role in vascular homeostasis is endothelin-1.…”

“…Keratinocytes produce it to constrict blood vessels, increase arterial blood pressure, and maintain vascular tone. Increased endothelin-1 production were as a cause of hypertension in psoriasis [ 15 , 24 ].…”

Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis

“…Another meta-analysis has also confirmed an elevated risk in the incidence of CVD including both coronary artery disease and even myocardial infarction linked to psoriasis in both European and East Asian populations [37]. Although this clinical phenomenon could be well explained by enhanced systemic inflammation led by activated immune cells, especially T cells, as well as a series of cytokines (e.g., TNF-α and IL-17) in both psoriasis and cardiometabolic disorders [38‒40], some recent studies have also noticed the role of metabolic abnormality in the immune-mediated pathogenesis of psoriasis [11, 15, 41]. As a special kind of metabolite that has proinflammatory effects, AGEs have been confirmed to be increased in both the serum and normal-appearing skin of psoriasis patients and decreased in the skin after effective treatment [22, 42‒44].…”

A Bibliometric Analysis of Global Research Trends in Psoriasis and Metabolic Syndrome

“…69,70 Concerning the genetic background, polymorphisms of the IL-23 gene are associated with the development or progression of CVD, whereas the polymorphisms of IL-12 and IL-17 gene are not. 71 The visceral adipose tissue can release several adipokines (resistin, leptin, and visfatin), cytokines (TNF-α, IL-6, and IL-8), and chemokines (monocyte chemoattractant protein 1, MCP-1), which encourage atherosclerosis. 72 Enhanced resistin and leptin levels activate inflammatory cytokines, thereby initiating and organizing vascular inflammation.…”