Schwarz Angelina, Qureshi Abdul Rashid, Hernandez Leah, Wennberg Lars, Wernerson Annika, Kublickiene Karolina, Shiels Paul G, Filograna Roberta, Stenvinkel Peter, Witasp Anna
Karolinska Institutet, Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, SE-141 52 Huddinge, Sweden.
Karolinska Institutet, Department of Clinical Science, Intervention and Technology, Division of Transplantation Surgery, SE-141 52 Huddinge, Sweden.
Cells. 2025 Jun 18;14(12):917. doi: 10.3390/cells14120917.
Patients with chronic kidney disease (CKD) face an increased risk of early vascular aging, progressive vascular calcification, and premature death. With increasing age, mitochondrial function and mitochondrial DNA copy number (mtDNA-cn) decline. This has been identified as an independent predictor of frailty and mortality in cardiovascular diseases (CVDs) and cancer. However, the relationship between mtDNA-cn and vascular calcification in the context of a uremic milieu remains ambiguous. We hypothesize that a lower mtDNA-cn is associated with medial calcification, as both are linked to impaired vascular health and accelerated aging. mtDNA-cn was analyzed in 211 CKD5 patients undergoing renal transplantation (RTx) and 196 healthy controls using quantitative PCR (qPCR) for three mtDNA genes (, , and ) and single-locus nuclear gene hemoglobin beta (). In 32 patients, mtDNA-cn was also quantified one year after RTx. The association between mtDNA-cn and vascular calcification scores, circulatory cell-free (ccf) mtDNA in plasma, and the surrogate marker of biological aging (skin autofluorescence) and CVD risk was assessed. mtDNA-cn was significantly lower in CKD5 patients than in controls and correlated with biological age, vascular calcification, and CVD risk. One year after RTx there was a significant recovery of mtDNA-cn in male patients compared to baseline levels. mtDNA-cn and ccf-mtDNA were inversely correlated. This prospective study provides novel insights into the link between low mtDNA-cn and vascular aging. It demonstrates that RTx restores mtDNA levels and may improve oxidative phosphorylation capacity in CKD. Further investigation is warranted to evaluate mtDNA as a biologically relevant biomarker and a potential therapeutic target for early vascular aging in the uremic environment.
慢性肾脏病（CKD）患者面临早期血管衰老、进行性血管钙化和过早死亡风险增加的问题。随着年龄增长，线粒体功能和线粒体DNA拷贝数（mtDNA-cn）会下降。这已被确定为心血管疾病（CVD）和癌症中衰弱和死亡的独立预测因子。然而，在尿毒症环境中，mtDNA-cn与血管钙化之间的关系仍不明确。我们假设较低的mtDNA-cn与中膜钙化有关，因为两者都与血管健康受损和加速衰老有关。使用定量PCR（qPCR）对三个mtDNA基因（、、和）以及单基因座核基因血红蛋白β（），分析了211例接受肾移植（RTx）的CKD5患者和196例健康对照的mtDNA-cn。在32例患者中，还在RTx一年后对mtDNA-cn进行了定量。评估了mtDNA-cn与血管钙化评分、血浆中循环游离（ccf）mtDNA、生物衰老替代标志物（皮肤自发荧光）和CVD风险之间的关联。CKD5患者的mtDNA-cn显著低于对照组，且与生物学年龄、血管钙化和CVD风险相关。与基线水平相比，男性患者在RTx一年后mtDNA-cn有显著恢复。mtDNA-cn与ccf-mtDNA呈负相关。这项前瞻性研究为低mtDNA-cn与血管衰老之间的联系提供了新的见解。它表明RTx可恢复mtDNA水平，并可能改善CKD患者的氧化磷酸化能力。有必要进一步研究以评估mtDNA作为生物学相关生物标志物以及尿毒症环境中早期血管衰老潜在治疗靶点的作用。
