Stromal Cell-Derived Factor-1, P-Selectin, and Advanced Oxidation Protein Products with Mitochondrial Dysfunction Concurrently Impact Cerebral Vessels in Patients with Normoalbuminuric Diabetic Kidney Disease and Type 2 Diabetes Mellitus

被引：0

作者：

Petrica, Ligia ^{[1
,2
,3
,4
,5
]}

Gadalean, Florica ^{[1
,2
,5
]}

Vlad, Adrian ^{[2
,3
,4
,5
,6
]}

Muntean, Danina Mirela ^{[2
,4
,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-Marcu, 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
]}

Jianu, Dragos Catalin ^{[2
,3
,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, Ctr Translat Res & Syst Med, Fac Med, 2 Eftimie Murgu Sq, Timisoara 300041, Romania

[5] Cty Emergency Hosp Timisoara, Timisoara 300723, Romania

[6] Victor Babes Univ Med & Pharm, Dept Internal Med 2, Div Diabet Nutr & Metab Dis, 2 Eftimie Murgu Sq, Timisoara 300041, Romania

[7] Victor Babes Univ Med & Pharm, Dept Funct Sci 3, Div Pathophysiol, 2 Eftimie Murgu Sq, Timisoara 300041, Romania

[8] Victor Babes Univ Med & Pharm, Dept Biochem & Pharmacol 4, 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 Neurosci 8, Div Neurol 1, 2 Eftimie Murgu Sq, Timisoara 300041, Romania

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2025年 / 26卷 / 10期

关键词：

stromal cell-derived factor-1; P-selectin; advanced oxidation protein products; cerebral vessels; diabetic kidney disease; INTIMA-MEDIA THICKNESS; CAROTID-ARTERY; CEREBROVASCULAR REACTIVITY; ENDOTHELIAL DYSFUNCTION; CXCL12; PLASMA; ATHEROSCLEROSIS; EXPRESSION; CHEMOKINE; MARKERS;

D O I：

10.3390/ijms26104481

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：

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-beta-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms.

引用

页数：20

共 63 条

[1] The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques [J].