Importance: Psoriasis is a common autoinflammatory disease influenced by complex interactions between environmental and genetic factors. The influence of long-term air pollution exposure on psoriasis remains underexplored.Objective: To examine the association between long-term exposure to air pollution and psoriasis and the interaction between air pollution and genetic susceptibility for incident psoriasis.Design, Setting, and Participants: This prospective cohort study used data from the UK Biobank. The analysis sample included individuals who were psoriasis free at baseline and had available data on air pollution exposure. Genetic analyses were restricted to White participants. Data were analyzed between November 1 and December 10, 2023.Exposures: Exposure to nitrogen dioxide (NO₂), nitrogen oxides (NO_x), fine particulate matter with a diameter less than 2.5 µm (PM_2.5), and particulate matter with a diameter less than 10 µm (PM₁₀) and genetic susceptibility for psoriasis.Main Outcomes and Measures: To ascertain the association of long-term exposure to NO₂, NO_x, PM_2.5, and PM₁₀ with the risk of psoriasis, a Cox proportional hazards model with time-varying air pollution exposure was used. Cox models were also used to explore the potential interplay between air pollutant exposure and genetic susceptibility for the risk of psoriasis incidence.Results: A total of 474 055 individuals were included, with a mean (SD) age of 56.54 (8.09) years and 257 686 (54.36%) female participants. There were 9186 participants (1.94%) identified as Asian or Asian British, 7542 (1.59%) as Black or Black British, and 446 637 (94.22%) as White European. During a median (IQR) follow-up of 11.91 (11.21-12.59) years, 4031 incident psoriasis events were recorded. There was a positive association between the risk of psoriasis and air pollutant exposure. For every IQR increase in PM_2.5, PM₁₀, NO₂, and NO_x, the hazard ratios (HRs) were 1.41 (95% CI, 1.35-1.46), 1.47 (95% CI, 1.41-1.52), 1.28 (95% CI, 1.23-1.33), and 1.19 (95% CI, 1.14-1.24), respectively. When comparing individuals in the lowest exposure quartile (Q1) with those in the highest exposure quartile (Q4), the multivariate-adjusted HRs were 2.01 (95% CI, 1.83-2.20) for PM_2.5, 2.21 (95% CI, 2.02-2.43) for PM₁₀, 1.64 (95% CI, 1.49-1.80) for NO₂, and 1.34 (95% CI, 1.22-1.47) for NO_x. Moreover, significant interactions between air pollution and genetic predisposition for incident psoriasis were observed. In the subset of 446 637 White individuals, the findings indicated a substantial risk of psoriasis development in participants exposed to the highest quartile of air pollution levels concomitant with high genetic risk compared with those in the lowest quartile of air pollution levels with low genetic risk (PM_2.5: HR, 4.11; 95% CI, 3.46-4.90; PM₁₀: HR, 4.29; 95% CI, 3.61-5.08; NO₂: HR, 2.95; 95% CI, 2.49-3.50; NO_x: HR, 2.44; 95% CI, 2.08-2.87).Conclusions and Relevance: In this prospective cohort study of the association between air pollution and psoriasis, long-term exposure to air pollution was associated with increased psoriasis risk. There was an interaction between air pollution and genetic susceptibility on psoriasis risk.

Background: Cardiac remodeling predisposes individuals to heart failure if the burden is not solved, and heart failure is a growing cause of morbidity and mortality worldwide. The cardiac extracellular matrix not only provides structural support, but also is a core aspect of the myocardial response to various biomechanical stresses and heart failure. MFAP4 (microfibrillar‐associated protein 4) is an integrin ligand located in the extracellular matrix, whose biological functions in the heart remain poorly understood. In the current study we aimed to test the role of MFAP4 in cardiac remodeling. Methods and Results: MFAP4‐deficient (MFAP4 ^−/− ) and wild‐type mice were subjected to aortic banding surgery and isoproterenol to establish models of cardiac remodeling. We also evaluated the functional effects of MFAP4 on cardiac hypertrophy, fibrosis, and cardiac electrical remodeling. The expression of MFAP4 was increased in the animal cardiac remodeling models induced by pressure overload and isoproterenol. After challenge of 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol, MFAP4 ^−/− mice exhibited lower levels of cardiac fibrosis and fewer ventricular arrhythmias than wild‐type mice. However, there was no significant effect on cardiomyocyte hypertrophy. In addition, there was no significant difference in cardiac fibrosis severity, hypertrophy, or ventricular arrhythmia incidence between wild‐type‐sham and knockout‐sham mice. Conclusions: These findings are the first to demonstrate that MFAP4 deficiency inhibits cardiac fibrosis and ventricular arrhythmias after challenge with 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol but does not significantly affect the hypertrophy response. In addition, MFAP4 deficiency had no significant effect on cardiac fibrosis, hypertrophy, or ventricular arrhythmia in the sham group in this study.