Hypertension Associated With Hyperlipidemia Induced Different MicroRNA Expression Profiles in Plasma, Platelets, and Platelet-Derived Microvesicles; Effects of Endothelial Progenitor Cell Therapy

Abstract

Aim: The aim of this study was to analyze the expressed profiles of miRNAs in plasma, platelets, and platelet-derived microvesicles (PMVs) obtained from experimental induced atherosclerosis animal model and to investigate the effect of EPC transplantation on these profiles.Methods: Seventeen selected circulating miRNAs (miR-19a,-21,-126,-146a,-223,-26b,-92a,-222,-210,-221,-143,-10a,-145,-155,-34a,-204, and miR-214) were individually analyzed in plasma, platelets, and PMVs isolated from peripheral blood of hypertensive-hyperlipidemic hamsters treated or not with endothelial progenitor cells (EPCs), and of healthy hamsters taken as control group.Results: Comparative with control group, in hypertension associated with hyperlipidemia the investigated miRNA expression profiles were different: (i) in plasma, the levels of all investigated miRNAs were significantly increased, the highest enhances being noticed for miR-21,-146a,-221,-143,-34a, and miR-204; (ii) in platelets, the expressions of almost all miRNAs were significantly elevated, remarkable for miR-126,-146a,-223,-222, and miR-214, while levels of miR-143, miR-10a, and miR-145 were significantly reduced; (iii) in PMVs, numerous miRNAs were found to have significantly increased levels, especially miR-222,-221,-210, and miR-34a, whereas expressions of various miRNAs as miR-223,-214,-146a,-143,-10a, and miR-145 were significantly decreased. The treatment with EPCs had the following reverse effects: (i) in plasma, significantly reduced the expression of miR-26b,-143,-34a,-204, and miR-214; (ii) in platelets, significantly decreased the levels of almost investigated miRNAs, with remarkably diminishing for miR-126 and miR-221; and (iii) in PMVs, significantly lowered the expression of some miRNAs, with considerably reductions for miR-222,-221,-210, and miR-19a, while the level of miR-214 was found elevated.Conclusions: The present study revealed that miRNAs have differential expression profiles in plasma, platelets, and PMVs under hypertension associated with hyperlipidemia conditions. The different miRNA profile in PMVs compared with platelets indicated an active mechanism of selective packing of miRNAs into PMVs from maternal cells; various miRNAs such as miR-19a,-21,-126,-26b,-92a,-155,-204,-210,-221,-222, and−34a delivered by PMVs may contribute to enrichment of circulating plasma miRNA expression. In addition, our study showed that the EPC-based therapy can regulate the expressions of investigated miRNAs into the three sources. These results provide novel information that could help in finding potential targets for the development of new therapeutic strategies in the cardiovascular disease.

MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

“…Hypertension along with hyperlipidemia was also found to influence the expression of various platelet-related miRNAs, out of which miR-126, miR-146a, miR-223, and miR-214 were found to be significantly upregulated, while miR-143, miR-10a, and miR-145 were downregulated in platelets. Simultaneously, miR-222, miR-221, miR-34a, and miR-210 levels were increased, while miR-223 levels together with miR-146a, miR-214, miR-143, and miR-145 were decreased in PEVs (Alexandru et al, 2019). These findings are based mainly on animal studies, and further clinical research is needed to confirm their results.…”

MiR-223-3p in Cardiovascular Diseases: A Biomarker and Potential Therapeutic Target

“…The characteristics of miRNAs, which can be easily acquired from plasma or serum in patients and conveniently detected by commonly used techniques, make it an important potential biomarker in multiple diseases (8,65). Circulating levels of miR-223-3p have been associated with atherosclerotic diseases and hyperlipidemia (35,(66)(67)(68). It was found that miR-223-3p levels were elevated in serum and atherosclerotic vessels of patients with atherosclerosis, as well as atherosclerotic models established in apolipoprotein E deficient mice (35).…”

“…It was found that miR-223-3p levels were elevated in serum and atherosclerotic vessels of patients with atherosclerosis, as well as atherosclerotic models established in apolipoprotein E deficient mice (35). Hypertension associated with hyperlipidemia, as the major risk factor leading to atherosclerotic diseases, could mimic the atherosclerotic situation and increase the plasma and platelet levels of miR-223-3p but reduced the levels in platelet-derived microvesicles in hamsters (68). However, other research indicated that plasma miR-223-3p levels were reduced in patients with abdominal aortic aneurysm, an atherosclerosis-related disease (66).…”

Membrane Microvesicles as Potential Vaccine Candidates

“…MVs play an essential role in cellular communication in physiological and pathological conditions, contributing to the pathogenesis of inflammation [ 88 , 89 , 90 , 91 , 92 , 93 , 94 ], coagulation [ 88 , 95 , 96 , 97 ], immunomodulation [ 93 ], regeneration [ 98 , 99 , 100 , 101 ] and tumorigenesis [ 76 , 102 ]. MV contribution to pathogenesis is often achieved through delivering cytokines, chemokines, mRNA and miRNA between cells [ 103 , 104 ]. Thus, MVs are considered as potential biomarkers in various diseases [ 69 , 105 , 106 ].…”

“…The ability of MVs to deliver cargo is an attractive model for the delivery of therapeutics to sites commonly hard to access via conventional delivery routes [ 58 , 104 ]. For example, Tang et al have assessed the delivery potential of tumor-derived MVs when used to transport chemotherapeutic drugs [ 66 ].…”