Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY 40208, USA.
Int J Mol Sci. 2021 Jan 30;22(3):1383. doi: 10.3390/ijms22031383.
Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine) which supports physiological homeostasis by buffering intracellular pH, chelating metals, and conjugating with and neutralizing toxic aldehydes such as acrolein. However, it is not clear if carnosine can support cardiovascular function or modify cardiovascular disease (CVD) risk. To examine this, we measured urinary levels of nonconjugated carnosine and its acrolein conjugates (carnosine-propanal and carnosine-propanol) in participants of the Louisville Healthy Heart Study and examined associations with indices of CVD risk. We found that nonconjugated carnosine was significantly associated with hypertension ( = 0.011), heart failure ( = 0.015), those categorized with high CVD risk ( < 0.001), body mass index (BMI; = 0.007), high sensitivity C-reactive protein (hsCRP; = 0.026), high-density lipoprotein (HDL; = 0.007) and certain medication uses. Levels of carnosine-propanal and carnosine-propanol demonstrated significant associations with BMI, blood glucose, HDL and diagnosis of diabetes. Carnosine-propanal was also associated with heart failure ( = 0.045) and hyperlipidemia ( = 0.002), but no associations with myocardial infarction or stroke were identified. We found that the positive associations of carnosine conjugates with diabetes and HDL remain statistically significant ( < 0.05) in an adjusted, linear regression model. These findings suggest that urinary levels of nonconjugated carnosine, carnosine-propanal and carnosine-propanol may be informative biomarkers for the assessment of CVD risk-and particularly reflective of skeletal muscle injury and carnosine depletion in diabetes.
肌肽是一种天然存在的二肽（β-丙氨酸-L-组氨酸），通过缓冲细胞内 pH 值、螯合金属以及与有毒醛（如丙烯醛）结合并中和来支持生理内稳态。然而，目前尚不清楚肌肽是否可以支持心血管功能或改变心血管疾病（CVD）风险。为了研究这一点，我们在路易斯维尔健康心脏研究（Louisville Healthy Heart Study）的参与者中测量了尿中非结合肌肽及其丙烯醛结合物（肌肽丙醛和肌肽丙醇）的水平，并研究了它们与 CVD 风险指数的关联。我们发现，非结合肌肽与高血压（ = 0.011）、心力衰竭（ = 0.015）、高 CVD 风险分类（ < 0.001）、体重指数（BMI； = 0.007）、高敏 C 反应蛋白（hsCRP； = 0.026）、高密度脂蛋白（HDL； = 0.007）和某些药物的使用显著相关。肌肽丙醛和肌肽丙醇的水平与 BMI、血糖、HDL 和糖尿病诊断显著相关。肌肽丙醛还与心力衰竭（ = 0.045）和高脂血症（ = 0.002）相关，但与心肌梗死或中风无关。我们发现，在调整后的线性回归模型中，肌肽结合物与糖尿病和 HDL 的正相关仍然具有统计学意义（ < 0.05）。这些发现表明，尿中非结合肌肽、肌肽丙醛和肌肽丙醇的水平可能是评估 CVD 风险的信息生物标志物，特别是反映糖尿病患者的骨骼肌损伤和肌肽耗竭。
