Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk
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 func...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/3/1383 |
| _version_ | 1797405862305726464 |
|---|---|
| author | Timothy E. O’Toole Xiaohong Li Daniel W. Riggs David J. Hoetker Shahid P. Baba Aruni Bhatnagar |
| author_facet | Timothy E. O’Toole Xiaohong Li Daniel W. Riggs David J. Hoetker Shahid P. Baba Aruni Bhatnagar |
| author_sort | Timothy E. O’Toole |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.011), heart failure (<i>p</i> = 0.015), those categorized with high CVD risk (<i>p</i> < 0.001), body mass index (BMI; <i>p</i> = 0.007), high sensitivity C-reactive protein (hsCRP; <i>p</i> = 0.026), high-density lipoprotein (HDL; <i>p</i> = 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 (<i>p</i> = 0.045) and hyperlipidemia (<i>p</i> = 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-09T03:16:24Z |
| format | Article |
| id | doaj.art-d777fb9c3ec94e88bcdb8c809f76a413 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:16:24Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d777fb9c3ec94e88bcdb8c809f76a4132023-12-03T15:19:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223138310.3390/ijms22031383Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease RiskTimothy E. O’Toole0Xiaohong Li1Daniel W. Riggs2David J. Hoetker3Shahid P. Baba4Aruni Bhatnagar5Department of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY 40202, USAChristina Lee Brown Envirome Institute, University of Louisville, Louisville, KY 40208, USADepartment of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, University of Louisville, Louisville, KY 40202, USACarnosine 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 (<i>p</i> = 0.011), heart failure (<i>p</i> = 0.015), those categorized with high CVD risk (<i>p</i> < 0.001), body mass index (BMI; <i>p</i> = 0.007), high sensitivity C-reactive protein (hsCRP; <i>p</i> = 0.026), high-density lipoprotein (HDL; <i>p</i> = 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 (<i>p</i> = 0.045) and hyperlipidemia (<i>p</i> = 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 (<i>p</i> < 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.https://www.mdpi.com/1422-0067/22/3/1383carnosineacroleincardiovascular diseasebiomarker |
| spellingShingle | Timothy E. O’Toole Xiaohong Li Daniel W. Riggs David J. Hoetker Shahid P. Baba Aruni Bhatnagar Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk International Journal of Molecular Sciences carnosine acrolein cardiovascular disease biomarker |
| title | Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk |
| title_full | Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk |
| title_fullStr | Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk |
| title_full_unstemmed | Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk |
| title_short | Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk |
| title_sort | urinary levels of the acrolein conjugates of carnosine are associated with cardiovascular disease risk |
| topic | carnosine acrolein cardiovascular disease biomarker |
| url | https://www.mdpi.com/1422-0067/22/3/1383 |
| work_keys_str_mv | AT timothyeotoole urinarylevelsoftheacroleinconjugatesofcarnosineareassociatedwithcardiovasculardiseaserisk AT xiaohongli urinarylevelsoftheacroleinconjugatesofcarnosineareassociatedwithcardiovasculardiseaserisk AT danielwriggs urinarylevelsoftheacroleinconjugatesofcarnosineareassociatedwithcardiovasculardiseaserisk AT davidjhoetker urinarylevelsoftheacroleinconjugatesofcarnosineareassociatedwithcardiovasculardiseaserisk AT shahidpbaba urinarylevelsoftheacroleinconjugatesofcarnosineareassociatedwithcardiovasculardiseaserisk AT arunibhatnagar urinarylevelsoftheacroleinconjugatesofcarnosineareassociatedwithcardiovasculardiseaserisk |