Quantitative proteomic analysis of human serum using tandem mass tags to predict cardiovascular risks in patients with psoriasis

Abstract

Although biomarker candidates associated with psoriasis have been suggested, those for predicting the risk of cardiovascular disease (CVD) early in patients with psoriasis are lacking. We aimed to identify candidate biomarkers that can predict the occurrence of CVD in psoriasis patients. We pursued quantitative proteomic analysis of serum samples composed of three groups: psoriasis patients with and those without CVD risk factors, and healthy controls. Age/Sex-matched serum samples were selected and labeled with 16-plex tandem mass tag (TMT) and analyzed using liquid chromatography-mass spectrometry and subsequent verification with ELISA. Of the 184 proteins that showed statistical significance (P-value < 0.05) among the three groups according to TMT-based quantitative analysis, 98 proteins showed significant differences (> 2.0-fold) between the psoriasis groups with and without CVD risk factors. Verification by ELISA revealed that caldesmon (CALD1), myeloid cell nuclear differentiation antigen (MNDA), and zyxin (ZYX) levels were significantly increased in the psoriasis group with CVD risk factors. Further network analysis identified pathways including integrin signaling, which could be related to platelet aggregation, and actin cytoskeleton signaling. Three novel candidates (MNDA, ZYX, and CALD1) could be potential biomarkers for predicting CVD risks in psoriasis patients. We expect these biomarker candidates can be used to predict CVD risk in psoriasis patients in clinical settings although further studies including large validation are needed.

Functional mutation, splice, distribution, and divergence analysis of impactful genes associated with heart failure and other cardiovascular diseases

“…These genes included ATP2A2 , CD34 , CD40LG , DDX41 , FADD , FGF2 , FLNA , HBA1 , KANTR , MB , SLC2A1 , TAC1 , and ZBTB8OS . Previous literature has linked CALD1, TEK, TRPV1, ATP2A2 , and SMUG1 to CVDs, supporting the findings from our functional mutation analysis 57 – 61 . Further research must be conducted to solidify these claims regarding the significance of these genes.…”

Platelet activation: a promoter for psoriasis and its comorbidity, cardiovascular disease

“…Kotowicz et al found expressions of adhesion molecules in endothelial cells, including ICAM-1, VCAM-1 and E-selectin, were significantly enhanced by stimulation with CD40L (132), which was usually located in the membrane of activated platelets and bound with CD40 on endothelial cells to function. On the other hand, Kim et al confirmed that integrin was the one of the most important proteins in the psoriasis group with high CVD risk through GO and IPA analysis (19). Consistent with this, the b1 and b2 integrindependent affinity of monocyte/macrophage to ICAM-1 and VCAM-1 on endothelial cells is enhanced by plateletinduced LTB 4 and accelerate the adhesion of monocyte/ macrophage to endothelium in atherosclerotic plaque (133).…”

“…On the other hand, Kim et al. confirmed that integrin was the one of the most important proteins in the psoriasis group with high CVD risk through GO and IPA analysis ( 19 ). Consistent with this, the β1 and β2 integrin-dependent affinity of monocyte/macrophage to ICAM-1 and VCAM-1 on endothelial cells is enhanced by platelet-induced LTB 4 and accelerate the adhesion of monocyte/macrophage to endothelium in atherosclerotic plaque ( 133 ).…”

“…On the other hand, platelet dysfunction is involved in the pathogenesis of CVD including atherosclerosis, coronary thrombosis, stroke, and MI ( 17 , 18 ). A Gene Ontology (GO) enrichment analysis showed that platelet aggregation and platelet activation terms were in the top five biological process terms in the psoriasis group with CVD risk factors ( 19 ), highlighting the important role of platelets in psoriasis-associated CVD.…”