microRNAs involved in psoriasis and cardiovascular diseases

Abstract

Psoriasis is a chronic inflammatory disease involving the skin. Both genetic and environmental factors play a pathogenic role in psoriasis and contribute to the severity of the disease. Psoriasis, in fact, has been associated with different comorbidities such as diabetes, metabolic syndrome, gastrointestinal or kidney diseases, cardiovascular disease (CVD), and cerebrovascular diseases (CeVD). Indeed, life expectancy in severe psoriasis is reduced by up to 5 years due to CVD and CeVD. Moreover, patients with severe psoriasis have a higher prevalence of traditional cardiovascular (CV) risk factors, including dyslipidemia, diabetes, smoking, and hypertension. Further, systemic inflammation is associated with oxidative stress increase and induces endothelial damage and atherosclerosis progression. Different miRNA have been already described in psoriasis, both in the skin tissues and in the blood flow, to play a role in the progression of disease. In this review, we will summarize and discuss the most important miRNAs that play a role in psoriasis and are also linked to CVD.

Keywords: cardiovascular diseases; microRNAs; psoriasis.

Figure 1

miR-200c in psoriasis and CVD. miR-200c is upregulated by reactive oxygen species (ROS) and is responsible for apoptosis, senescence, endothelial dysfunction, ROS increase and nitric oxide decrease, all features associated with atherosclerosis. Indeed, miR-200c increases in carotid plaques and plasma of atherosclerotic patients vs healthy subjects and positively correlates with plaque instability biomarkers (i.e. MCP1, IL6, COX2, MMP1, MMP9 and miR-33) and negatively with stability biomarkers (i.e. SIRT1, FOXO1, eNOS and ZEB1). ROS modulation, endothelial dysfunction, cardiac remodeling and inflammation are also associated with psoriasis. Iin keeping with this, miR-200c is increased in LS vs NL and vs HS, and in plasma of psoriatic patients. miR-200c correlates with PASI and the duration of disease and with determinants of CVD (i.e. LV mass, E/e’ and RWT) in psoriatic patients.

Figure 2

miR-200c and miR-33 interplay in psoriasis and CVD. miR-200c and miR-33 positively correlate in plasma and plaques of atherosclerotic patients. A molecular mechanism among miR-33a/b and miR-200c increase does exist. Indeed, the overexpression of miR-33a/b in vitro in different cells (i.e. ECs, hepatic cells and embryonic kidney cells) causes the intracellular and extracellular increase of miR-200c via a ZEB1-decrease mechanism. ZEB1, in fact, is a direct target of both miR-33 and miR-200c and a transcriptional inhibitor of miR-200c. Hence, a ZEB1-decrease causes upregulation of both intracellular and extracellular miR-200c expression levels. An increase of miR-200c in skin plaques and plasma of psoriatic patients was also observed, and it positively correlates with PASI index and determinants of CVD risk (RWT, E/e’ and LV mass). Interestingly, miR-33a was found to be upregulated in the plasma of psoriatic patients and positively correlates with HOMA-insulin resistance index and cIMT. Therefore, a possible link in psoriasis could also exist among miR-33 and miR-200c, contributing to the increase of CVD in these patients.