Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk

Abstract

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 (p = 0.011), heart failure (p = 0.015), those categorized with high CVD risk (p < 0.001), body mass index (BMI; p = 0.007), high sensitivity C-reactive protein (hsCRP; p = 0.026), high-density lipoprotein (HDL; p = 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 (p = 0.045) and hyperlipidemia (p = 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 (p < 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.

Anti-cancer actions of carnosine and the restoration of normal cellular homeostasis

“…Many years ago carnosine was shown (in a model system) to protect proteins against MG-mediated modification, by presumably reacting directly with MG [60]. However, the expected carnosine-MG adduct has not been detected in vivo, whereas adducts between carnosine and propanal, propanol and acrolein have been found in human tissues [40,61], suggesting (speculatively) that the putative carnosine-MG adduct might be their precursor via the activity of unidentified aldoketo-reductases.…”

Comparative evaluation of different modalities for measuring in vivo carnosine levels

“…Given the potential therapeutic utility of exogenously delivered carnosine and it wide-ranging role in physiological homeostasis, quantitative measures of this di-peptide or its conjugates in different tissues and cellular compartments could be used as an indirect assessment of individual levels of oxidative stress, inflammation, and health risk [ 24 , 25 ], as well as an index of the efficacy of supplementation. However many prior studies do little to evaluate this, nor is it clear how best to do this or what tissue source of carnosine to measure.…”

“…Although carnosine is mostly stored in skeletal, it is also excreted in urine, where its levels can be accurately measured by high-performance LC/MS/MS [ 24 , 25 , 34 ]. Carnosine is also present in blood, but it is readily hydrolyzed into L-histidine and β-alanine by serum carnosinase, making it difficult to measure, even in the setting of chronic oral supplementation [ 35 , 36 ].…”

Microfluidics for diagnosis and treatment of cardiovascular disease

“…5 This definition points out that biomarker is an indicator that can be quantified. For example, urinary carnosine–acrolein complex is significantly correlated with the presence of CVD risk factors, 6 and blood troponin is significantly elevated in patients with myocardial infarction. 7 Therefore, the detection of CVD markers is of great significance for disease diagnosis and treatment, and has great application potential in the clinical diagnosis of CVD.…”