Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes.
Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes.
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DOI：
10.1161/circresaha.116.309421
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发表时间：
2017-03-31
影响因子：
20.1
通讯作者：
Vaccarino V
中科院分区：
文献类型：
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作者：
Hammadah M;Al Mheid I;Wilmot K;Ramadan R;Abdelhadi N;Alkhoder A;Obideen M;Pimple PM;Levantsevych O;Kelli HM;Shah A;Sun YV;Pearce B;Kutner M;Long Q;Ward L;Ko YA;Hosny Mohammed K;Lin J;Zhao J;Bremner JD;Kim J;Waller EK;Raggi P;Sheps D;Quyyumi AA;Vaccarino V
白细胞端粒长度（LTL）是衰老的生物学标志，较短的LTL与不良心血管结局相关。已提出降低再生能力作为一种机制。骨髓来源的循环祖细胞（PC）参与组织修复和再生。研究LTL和PC之间的关系及其对不良心血管结局的影响。我们采用定量PCR方法检测了566例门诊冠心病患者（年龄63±9岁，76%为男性）的LTL。通过流式细胞术计数循环PC。校正年龄、性别、种族、BMI、吸烟和既往心肌梗死后，LTL缩短与CD 34+细胞计数降低相关：LTL每缩短10%，CD 34+水平降低5.2%（p<0.001）。校正上述因素后，短LTL（<Q1）和低CD 34+水平（<Q1）均预测不良心血管结局（死亡、心肌梗死、冠状动脉血运重建或脑血管事件），风险比（HR）为1.8，95%置信区间（CI）为1.1-2.0，HR为2.1，95% CI，1.3-3.0，分别比较Q1和Q2-4。同时具有短LTL（<Q1）和低CD 34+细胞计数（<Q1）的患者具有最大的不良结局风险（HR=3.5，95% CI，1.7-7.1）。尽管LTL缩短与再生能力降低相关，但LTL和循环PC水平均是CAD患者不良心血管结局的独立和附加预测因子。我们的研究结果表明，生物老化和再生能力下降都有助于心血管事件，独立于传统的危险因素。
Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. To examine the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes. We measured LTL by quantitative PCR in 566 outpatients (age 63±9 years, 76% male) with coronary artery disease (CAD). Circulating PCs were enumerated by flow cytometry. After adjustment for age, gender, race, BMI, smoking and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (p<0.001). After adjustment for the aforementioned factors, both short LTL (<Q1) and low CD34+ levels (<Q1) predicted adverse cardiovascular outcomes (death, myocardial infarction, coronary revascularization or cerebrovascular events) independently of each other, with a hazards ratio (HR) of 1.8, 95% confidence interval (CI), 1.1–2.0, and a HR of 2.1, 95% CI, 1.3–3.0, respectively, comparing Q1 to Q2–4. Patients who had both short LTL (<Q1) and low CD34+ cell count (<Q1), had the greatest risk of adverse outcomes (HR=3.5, 95% CI, 1.7–7.1). Although shorter LTL is associated with decreased regenerative capacity, both LTL and circulating PC levels are independent and additive predictors of adverse cardiovascular outcomes in CAD patients. Our results suggest that both biological aging and reduced regenerative capacity contribute to cardiovascular events, independent of conventional risk factors.