Mitochondrial DNA and Inflammation Are Associated with Cerebral Vessel Remodeling and Early Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

被引:4
作者
Petrica, Ligia [1 ,2 ,3 ,4 ,5 ]
Gadalean, Florica [1 ,2 ,5 ]
Muntean, Danina Mirela [2 ,4 ,6 ]
Jianu, Dragos Catalin [2 ,3 ,5 ,7 ]
Vlad, Daliborca [2 ,5 ,8 ]
Dumitrascu, Victor [2 ,5 ,8 ]
Bob, Flaviu [1 ,2 ,5 ]
Milas, Oana [1 ,2 ,5 ]
Suteanu-Simulescu, Anca [1 ,2 ,5 ]
Glavan, Mihaela [1 ,2 ,5 ]
Ursoniu, Sorin [2 ,3 ,4 ,5 ,9 ]
Balint, Lavinia [1 ,2 ,5 ]
Mogos-Stefan, Maria [1 ,2 ,5 ]
Ienciu, Silvia [1 ,2 ,5 ]
Cretu, Octavian Marius [10 ,11 ]
Popescu, Roxana [2 ,5 ,12 ]
Gluhovschi, Cristina [1 ,2 ]
Iancu, Lavinia [1 ,2 ,5 ]
Vlad, Adrian [2 ,5 ,13 ]
机构
[1] Victor Babes Univ Med & Pharm, Dept Internal Med 2, Div Nephrol, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[2] Victor Babes Univ Med & Pharm, Fac Med, Ctr Mol Res Nephrol & Vasc Dis, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[3] Victor Babes Univ Med & Pharm, Fac Med, Ctr Cognit Res Neuropsychiat Pathol Neuropsy Cog, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[4] Victor Babes Univ Med & Pharm, Fac Med, Ctr Translat Res & Syst Med, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[5] Cty Emergency Hosp Timisoara, Timisoara 300723, Romania
[6] Victor Babes Univ Med & Pharm, Dept Funct Sci 3, Div Pathophysiol, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[7] Victor Babes Univ Med & Pharm, Dept Neurosciences8, Div Neurology1, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[8] Victor Babes Univ Med & Pharm, Dept Biochem & Pharmacology4, Div Pharmacol, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[9] Victor Babes Univ Med & Pharm, Dept Funct Sci 3, Div Publ Hlth & Hist Med, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[10] Victor Babes Univ Med & Pharm, Dept Surg 1, Div Surg Semiol 1, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[11] Emergency Clin Municipal Hosp Timisoara, Timisoara 300041, Romania
[12] Victor Babes Univ Med & Pharm, Dept Microscop Morphol 2, Div Cell & Mol Biol 2, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
[13] Victor Babes Univ Med & Pharm, Dept Internal Med 2, Div Diabet, 2,Eftimie Murgu Sq, Timisoara 300041, Romania
关键词
mitochondrial DNA; inflammation; cerebral vessels; diabetic kidney disease; CIRCULATING ADHESION MOLECULES; INTIMA-MEDIA THICKNESS; INTERNAL CAROTID-ARTERY; CORONARY-HEART-DISEASE; CEREBROVASCULAR REACTIVITY; COPY NUMBER; TNF-ALPHA; ATHEROSCLEROSIS; RISK; INTERLEUKIN-18;
D O I
10.3390/biom14040499
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-beta-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNF alpha), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNF alpha, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.
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页数:21
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