ABSTRACT
ABSTRACT: We investigated the clinical characteristics of patients with acute aortic dissection (AAD) and miR-590-3p levels in serum, tissue, and vascular smooth muscle cells. The effect of miR-590-3p on the vascular smooth muscle cell phenotype was assessed, and the regulation of lysyl oxidase by miR-5903p was determined. C57BL/6 mice were used to investigate the incidence of AAD and effects of miR-5903p on AAD. The miR-590-3p levels were measured in the aortae of mice, and hematoxylin and eosin staining and Masson staining were performed to identify the morphological features of the aorta. Comparative analysis revealed significant differences in clinical characteristics between patients with AAD and healthy control subjects, with most patients with AAD exhibiting concomitant hypertension and nearly 50% having atherosclerosis. Lysyl oxidase was a direct target of miR-590-3p. Lysyl oxidase overexpression inhibited switching of the vascular smooth muscle cell phenotype from contractile to synthetic, but miR-590-3p overexpression significantly reversed this change. In the mouse model, miR-590-3p upregulation increased the incidence of AAD to 93.3%, and its incidence decreased to 13.3% after miR-590-3p inhibition. Hematoxylin and eosin and Masson staining revealed that the miR-590-3p agomiR group had a greater loss of the contractile phenotype in the dissected aortic wall and an increased number of muscle fibers in the aortic wall, which contributed to thickening of the aortic wall and the formation of a false lumen in aortic dissection. miR-590-3p might be pivotal in the pathogenesis of AAD. Thus, targeting miR-590-3p or its downstream pathways could represent a therapeutic approach for AAD.
Subject(s)
Aortic Dissection , MicroRNAs , Animals , Humans , Mice , Aortic Dissection/genetics , Cell Proliferation , Cells, Cultured , Eosine Yellowish-(YS)/metabolism , Eosine Yellowish-(YS)/pharmacology , Hematoxylin/metabolism , Hematoxylin/pharmacology , Mice, Inbred C57BL , MicroRNAs/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Phenotype , Protein-Lysine 6-Oxidase/genetics , Protein-Lysine 6-Oxidase/metabolism , Protein-Lysine 6-Oxidase/pharmacologyABSTRACT
Mitochondrial DNA (MtDNA) mutations played an important role in the development of essential hypertension. Mitochondrial tRNA point mutations, caused the failure in tRNA metabolism, responsible for the pathogenesis of this complex disease. In this study, we evaluated the possible role of the 4329C >G mutation in the clinical expression of hypertension in a Chinese family. Analysis of the complete mtDNA sequence variants showed that other mutations may play synergic roles in the phenotypic manifestation of hypertension. In addition, other potential pitfalls were also discussed in this context.
Subject(s)
Asian People/genetics , DNA, Mitochondrial/genetics , Essential Hypertension/genetics , Mutation/genetics , Base Sequence , Family , Humans , RNA, Transfer/genetics , Sequence AlignmentABSTRACT
The goal of the work described here was to evaluate the role of virtual touch tissue quantification (VTQ) combined with urinary ß2-microglobulin (ß2-MG) measurement in the early diagnosis of gouty kidney damage. Two hundred fifty-nine patients with gouty kidney damage and 200 healthy control subjects were tested. The shear wave velocity (SWV) of the renal parenchyma and sinus as determined with VTQ and the urinary ß2-MG level of the two groups were analyzed. Although there were no significant differences in age, body mass index, creatinine level and blood urea nitrogen between the two groups (all p's > 0.05), the aforementioned parameters were higher in the group with gouty kidney damage than in the control group. Urinary ß2-MG levels of the patients with kidney damage were significantly higher than those of the control subjects (t = 6.38, p < 0.01). The SWV of the renal parenchyma was higher than that of the sinus in both groups. Compared with controls, patients with kidney damage had significantly increased renal parenchyma and sinus SWVs (all p-values < 0.05). Urinary ß2-MG level was positively linearly correlated with the SWV of renal parenchyma in patients with kidney damage (r = 0.442, p < 0.0001). However, there was no correlation between urinary ß2-MG level and the SWV of the sinus in patients with kidney damage (r = 0). In the control group, there was no correlation between urinary ß2-MG level and the SWV of the renal parenchyma or sinus. The elasticity of the kidney as determined with VTQ, combined with the urinary ß2-MG level, may be helpful in the early diagnosis of gouty kidney damage.
