Expressão de micro-rnas e transferência de colesterol in vitro hdl em acidente vascular cerebral por emergência hipertensiva

Abstract

Hypertensive crisis (HC) can account for damage on target organs characterizing hypertensive emergencies. Ischemic Stroke (IS) is among these injuries. Arterial stiffness, expression of microRNAs (miRNAs) and lipid metabolism are considered the possible factors related to HC. Objective – To evaluate the association of biochemical parameters, arterial stiffness, expression of miRNAs 221/222 and lipid transfer in IS patients presenting hypertensive emergency. Casuistics and Methods – A total of 128 individuals with hypertensive emergency IS = IS-HE (G1) and three control groups: individuals with non-hypertensive emergency IS = IS (G2); controlled hypertensive = CH (G3) and normotensive individuals = NT (G4). The diagnosis of IS was performed by computed tomography of the skull or magnetic resonance. Peripheral blood sample was collected for analysis of miRNAs expression by RT-q PCR (real-time quantitative polymerase chain reaction) and lipid transfer (lipid donor nanoemumulsion, radioactively labeled). Sociodemographic and anthropometric data were obtained by applying a questionnaire. Arterial stiffness was assessed using the Mobil-O-Graph® 24h PWA Monitor. Analysis of variance was applied for comparative study between the groups, admitting significance level for P-value <0.05. Results - Individuals from the IS-EH group were older (65 years) as compared to individuals from the NT group (56 years; P = 0.0002). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were higher in the IS-HE group than in the IS, CH and NT groups (P <0.0001 for all). Blood glucose was significantly higher in the IS-HE and IS groups compared to the NT group (P = 0.0045 and P = 0.0011; respectively). Creatinine was elevated in the IS-HE group as compared to CH (P = 0.0036). Total cholesterol was higher in the IS-HE compared to the CH group (P = 0.0319) and in the IS group as compared to the NT group (P = 0.0222). The low-density lipoprotein (LDL) was significantly higher in the IS-HE and NT groups as compared to the CH group (P = 0.0057 and P = 0.0009). Potassium levels were lower in the IS-HE and IS groups compared to the CH group (P = 0.0261 and P = 0.0492). Regarding central hemodynamic parameters, the central systolic and diastolic blood pressure of the IS-HE group were higher as compared to the CH and NT groups (P <0.0001 for all). IS also had higher central systolic and diastolic blood pressure as compared to the CH group (P = 0.0054; P <0.0001) and central SBP compared to NT (P = 0.0043). Augmentation index (Aix75) and pulse wave velocity (PWV) were higher in the IS-HE group than in the NT group (P = 0.0332 and P <0.0001; respectively). In the IS group, these variables were also higher compared to the NT group (P = 0.0003 and P = 0.0003; respectively). The miR-221 expression was higher in the IS-HE group showing significant difference as compared to the IS, CH and NT groups (P = 0.0030; P <0.0001 and P <0.0001; respectively). This same miRNA also showed overexpression in the IS group as compared to the CH and NT groups (P = 0.0118 and P = 0.0002). MiR-222 showed overexpression in the IS-HE, IS and NT groups compared to the CH group (P <0.0001 for all). According to the results of lipid transfer, it could be observed that the transfer of esterified cholesterol was reduced in the IS-HE group in relation to the IS and NT groups (P <0.05 for both). The IS group also showed decreased esterified cholesterol transfer compared to the NT group (P <0.001) and to the CH group (P <0.01). Non-esterified cholesterol transfer also exhibited a decrease in the IS-HE group compared to the IS, CH and NT groups (P <0.05; P <0.01 and P <0.001; respectively). The IS group also expressed lower levels of non-esterified cholesterol transfer compared to the CH and NT groups (P <0.01 and P <0.001; respectively). Regarding the correlations, there was a negative correlation between miR-221 and cholesterol ester transfer and miR-221 and free cholesterol. A negative correlation was also observed between cholesterol ester transfer and PWV and free cholesterol transfer and PWV. Conclusion - This study provides evidence of the miRNAs participation in the progression of hypertensive crisis, thus assuring that the increased expression of miR-221 and miR-222 determines a greater chance of the individual having a IS by HE. In addition, HE causes a marked decrease in lipid transfer to HDL. This reduction was previously associated with coronary heart disease. Therefore, HDL functions can be reduced in IS by HE, which can also contribute to atherogenesis.