Homocysteine Exposure Impairs Myocardial Resistance to Ischaemia Reperfusion and Oxidative Stress

Abstract

Background/Aims: Hyperhomocysteinaemia is recognised as a strong independent risk factor for developing cardiovascular disease. This study investigated how an acute homocysteine dose affected cardiac performance during ischaemia reperfusion and cardiomyocyte contractility and morphology under normal conditions and during oxidative stress. Methods: Cardiac function was measured in isolated and perfused rat hearts before and after 40 minutes' global normothermic ischaemia. Where used, 0.1 mM L-homocysteine was present prior to, and throughout ischaemia, before wash out after 10 minutes' reperfusion. Calcium transients under normal conditions and changes in contractile synchronicity during oxidative stress (exposure to 0.2 mM H₂O₂) were measured in freshly isolated rat cardiomyocytes incubated for 60 minutes ± 0.1 mM L-homocysteine. Results: During ischaemia reperfusion 0.1 mM L-homocysteine significantly reduced the rate pressure product during reperfusion (10,038 ± 749 vs. 5955 ± 567 mmHg bpm, p < 0.001), but did not affect time to ischaemic contracture. Incubation of freshly isolated cardiomyocytes with 0.1 mM L-homocysteine significantly decreased the amplitude of the calcium transient and slowed the time to half relaxation. Conclusions: These findings suggest that homocysteine exposure affected myocardial recovery from ischaemia and contractile homeostasis although the exact mechanisms for these changes remain to be determined.

Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage

“…Accumulated studies have indicated that Hcy as an intermediate metabolite of cysteine and methionine can cause endothelial dysfunction (Zhang et al, 2017 ). For instance, patients with hyperhomocysteinemia usually show decreased numbers of endothelial cells with impaired endothelial activities in endothelial proliferation, migration and adhesion, which all do harm to human heart health (Jamaluddin et al, 2007 ; Almashhadany et al, 2015 ). Experimentally, Hcy has been proved to be associated with disturbed cardiac substrate metabolism, mitochondrial dysfunction and adverse cardiac remodeling with increased myocardial stiffness (Joseph et al, 2003 ; Devi et al, 2006 ; Suematsu et al, 2007 ).…”

“…Homocysteine (Hcy) is an intermediate metabolite of cysteine and methionine. Large numbers of evidences have confirmed that elevated plasma levels of Hcy as an independent risk factor may induce endothelial dysfunction through oxidative stress and apoptosis, and eventually lead to the occurrence and development of human CVD (Almashhadany et al, 2015 ; Baggott and Tamura, 2015 ). However, Hcy-mediated toxicity toward cardiomyocytes was not well demonstrated, and the underlying mechanism remains elusive.…”

MTHFR C677T gene polymorphism and the severity of coronary lesions in acute coronary syndrome

“…[ 29 ] Moreover, HHcy was shown to lead to dysfunction and apoptosis of cardiomyocytes, an effect that was mediated via other signaling pathways, such as activation p38 MAPK. [ 30 , 31 ] Therefore, current evidence suggests that HHcy may aggravate CAD via its interaction with both the endothelial cells and cardiomyocytes.…”

Betaine in Inflammation: Mechanistic Aspects and Applications

“…Sulfur amino acids such as homocysteine, methionine, SAM, SAH, and cysteine are involved in various essential metabolic pathways, including GSH synthesis and protein synthesis, and transmethylation reactions. Although homocysteine contributes to GSH synthesis ( 51 ), various studies have demonstrated that hyperhomocysteinemia ultimately induces oxidative stress and apoptosis ( 52 , 53 ). Betaine treatment can directly influence homocysteine concentrations via stimulating homocysteine to form methionine to regulate SAA concentrations.…”