Abundance, localization, and functional correlates of the advanced glycation end‐product carboxymethyl lysine in human myocardium. Issue 20 (25th October 2017)

• Record Type: Journal Article
• Authors: LeWinter, Martin M.; Taatjes, Douglas; Ashikaga, Takamaru; Palmer, Bradley; Bishop, Nicole; VanBuren, Peter; Bell, Stephen; Donaldson, Cameron; Meyer, Markus; Margulies, Kenneth B.; Redfield, Margaret; Bull, David A.; Zile, Michael
• Is Part Of: Physiological reports. Volume 5:Issue 20(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-10-25
• Subjects: Advanced glycation end‐products -- carboxymethyl lysine -- diabetes mellitus -- hypertension -- myocardium; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13462
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Advanced glycation end‐products (AGEs) play a role in the pathophysiology of diabetes mellitus (DM) and possibly hypertension (HTN). In experimental DM, AGEs accumulate in myocardium. Little is known about AGEs in human myocardium. We quantified abundance, localization, and functional correlates of the AGE carboxymethyl lysine (CML) in left ventricular (LV) myocardium from patients undergoing coronary bypass grafting (CBG). Immunoelectron microscopy was used to quantify CML in epicardial biopsies from 98 patients (71 M, 27 F) with HTN, HTN + DM or neither (controls), all with normal LV ejection fraction. Myofilament contraction‐relaxation function was measured in demembranated myocardial strips. Echocardiography was used to quantify LV structure and function. We found that CML was abundant within cardiomyocytes, but minimally associated with extracellular collagen. CML counts/ μ m 2 were 14.7% higher in mitochondria than the rest of the cytoplasm ( P < 0.001). There were no significant sex or diagnostic group differences in CML counts [controls 45.6 ± 3.6/ μ m 2 (±SEM), HTN 45.8 ± 3.6/ μ m 2, HTN + DM 49.3 ± 6.2/ μ m 2 ; P = 0.85] and no significant correlations between CML counts and age, HgbA1c or myofilament function indexes. However, left atrial volume was significantly correlated with CML counts ( r = 0.41, P = 0.004). We conclude that in CBG patients CML is abundant within cardiomyocytes but minimally associated with collagen, suggesting that AGEs do not directly modify the stiffness of myocardial collagen. Coexistent HTN or HTN + DM do not significantly influence CML abundance. The correlation of CML counts with LAV suggests an influence on diastolic function independent of HTN, DM or sex whose mechanism remains to be determined. Abstract : We studied the abundance and localization of the advanced glycation end‐product carboxymethyl lysine (CML) in human myocardium in human myocardium obtained during coronary bypass grafting in patients with hypertension, hypertension + diabetes mellitus or neither (controls) using a quantitative, high resolution immunoelectron microscopic method. We found that CML was abundant in the cytoplasm of cardiomyocytes but very sparse in the extracellular matrix. CML counts did not differ between the three groups and were significantly correlated with left atrial volume, an index of diastolic function.