Key result
Experimental myocardial infarction in rats did not increase plasma AGE or RAGE levels, but decreased cardiac tissue AGEs and increased heart RAGE levels by 50% at 120 days.
Why the study?
Circulating AGE and RAGE are increased after MI and associated with worse clinical prognosis, but had never been characterized in an animal model of MI.
Does myocardial infarction induction alter AGE formation and RAGE expression in plasma and cardiac tissue in rats?
Does myocardial infarction induction alter AGE formation and RAGE expression in plasma and cardiac tissue in rats?
The rat MI model does not reflect clinical findings of increased plasma AGE or RAGE levels, suggesting caution when using this model to study the AGE-RAGE axis.
Rat MI model mismatches clinical AGE-RAGE changes; challenges its utility for this axis and leaves translational relevance open.
Circulating advanced glycation end products (AGE) and their receptor, RAGE, are increased after a myocardial infarction (MI) episode and seem to be associated with worse prognosis in patients. Despite the increasing importance of these molecules in the course of cardiac diseases, they have never been characterized in an animal model of MI. Thus, the aim of this study was to characterize AGE formation and RAGE expression in plasma and cardiac tissue during cardiac remodeling after MI in rats. Adult male Wistar rats were randomized to receive sham surgery (n = 15) or MI induction (n = 14) by left anterior descending coronary artery ligation. The MI group was stratified into two subgroups based on postoperative left ventricular ejection fraction: low (MIlowEF) and intermediate (MIintermEF). Echocardiography findings and plasma levels of AGEs, protein carbonyl, and free amines were assessed at baseline and 2, 30, and 120 days postoperatively. At the end of follow-up, the heart was harvested for AGE and RAGE evaluation. No differences were observed in AGE formation in plasma, except for a decrease in absorbance in MIlowEF at the end of follow-up. A decrease in yellowish-brown AGEs in heart homogenate was found, which was confirmed by immunodetection of N-ε-carboxymethyl-lysine. No differences could be seen in plasma RAGE levels among the groups, despite an increase in MI groups over the time. However, MI animals presented an increase of 50% in heart RAGE at the end of the follow-up. Despite the inflammatory and oxidative profile of experimental MI in rats, there was no increase in plasma AGE or RAGE levels. However, AGE levels in cardiac tissue declined. Thus, we suggest that the rat MI model should be employed with caution when studying the AGE-RAGE signaling axis or anti-AGE drugs for not reflecting previous clinical findings.
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Fracasso et al. (2019) studied Myocardial Infarction (n=29). Myocardial infarction induction (coronary artery ligation) vs. Sham surgery was evaluated on AGE formation and RAGE expression in plasma and cardiac tissue. Experimental myocardial infarction in rats did not increase plasma AGE or RAGE levels, but decreased cardiac tissue AGEs and increased heart RAGE levels by 50% at 120 days.
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