Mechanisms of Myocardial Damage Due to Hyperlipidemia: A Review of Recent Studies

Abstract

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.

Figure 1

Pathway diagram of hyperlipidemia leading to inflammatory response and oxidative stress. LDL – low density lipoprotein; FFA – free fatty acid; ROS – reactive oxygen species; SRC – tyrosine-protein kinase Src; RAS – GTPase HRas; ERK – mitogen-activated protein kinase; P38 – P38 mitogen-activated protein kinase; VAV – guanine nucleotide exchange factor VAV; Rac – Ras-related C3 botulinum toxin substrate; Lyn – tyrosine-proteon kinase Lyn; TXN – thierodexin; GSH – glutathione; oxLDL – oxidized low density lipoprotein; LOX-1 – lectin-like oxidized low-density lipoprotein receptor-1; RAGE – advanced glycation end product receptor; CD36 – CD36 antigen; LDLR – LDL receptor; PPARs – peroxisome proliferators-activated receptors; HO-1 – heme oxygenate-1; NQO-1 – quinine oxidoreductase 1; NF-κB – nuclear factor-κB; Nrf2 – nuclear factor erythroid 2-related factor 2; TNF-α – tumour necrosis factor alpha; IL – interleukin.

Figure 2

Pathway diagram of myocardial endoplasmic reticulum and mitochondria damage caused by hyperlipidemia. FFA – free fatty acid; ROS – reactive oxygen species; JNK – c-Jun N-terminal kinase; ATP – adenosine triphosphate; ER – endoplasmic reticulum; DRP1 – dynamin-related protein 1; AC – acetyl group; Bip – binding immunoglobulin protein; P – phosphoryl group; oxLDL – oxidized low density lipoprotein; PERK – double-stranded RNA-dependent protein kinase-like ER kinase; eIF2 – eukaryotic initation factor 2; IRE1 – inositol-requiring enzyme 1; Bcl-2 – B-cell lymphoma-2; CHOP – the C/EBP homologous protein; PPARs – peroxisome proliferators-activated receptors; NF-κB – nuclear factor-κB.