Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

Abstract

Heavy metals and metalloids like cadmium, arsenic, mercury, and lead are frequently found in the soil, water, food, and atmosphere; trace amounts can cause serious health issues to the human organism. These toxic trace elements (TTE) affect almost all the organs, mainly the heart, kidney, liver, lungs, and the nervous system, through increased free radical formation, DNA damage, lipid peroxidation, and protein sulfhydryl depletion. This work aims to advance our understanding of the mechanisms behind lipid accumulation via increased free fatty acid levels in circulation due to TTEs. The increased lipid level in the myocardium worsens the heart function. This dysregulation of the lipid metabolism leads to damage in the structure of the myocardium, inclusive fibrosis in cardiac tissue, myocyte apoptosis, and decreased contractility due to mitochondrial dysfunction. Additionally, it is discussed herein how exposure to cadmium decreases the heart rate, contractile tension, the conductivity of the atrioventricular node, and coronary flow rate. Arsenic may induce atherosclerosis by increasing platelet aggregation and reducing fibrinolysis, as exposure interferes with apolipoprotein (Apo) levels, resulting in the rise of the Apo-B/Apo-A1 ratio and an elevated risk of acute cardiovascular events. Concerning mercury and lead, these toxicants can cause hypertension, myocardial infarction, and carotid atherosclerosis, in association with the generation of free radicals and oxidative stress. This review offers a complete overview of the critical factors and biomarkers of lipid and TTE-induced cardiotoxicity useful for developing future protective interventions.

Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants’ Cellular Effects

“…The ERalfa at membrane caveolae associates with G proteins, NOS3, Src kinases, phosphoinositide 3-kinase (PI3K)/Akt, JAK/STAT, and MAPKs [84]. This cluster of proteins partially coincides with the rafts-associated protein network further described in Section 4 and can underlie changes in cytosolic calcium and cAMP levels, dysregulation of nitric oxide production, and MAPK, PI3K, JAK/STAT, or Src/STAT pathway activation, processes implicated in environmental toxicants' exposure, inflammation, and carcinogenesis [4,5,11,12,123,124]. These ER signalosome complexes could allow estrogen disruptors targeting lipid rafts to modify hormone signaling without direct interference with receptorhormone binding.…”

“…Exposure to ambient and diesel exhaust particulate matter (PM) and heavy metals like lead and mercury induces inflammation and endothelial/vascular dysfunction, which is associated with altered vasoconstriction/vasorelaxation and the development of atherosclerosis and cardiovascular diseases [ 5 , 12 , 14 ]. Noteworthy, proteins controlling Ca 2+ signaling and the endothelial nitric oxide synthase (eNOS or NOS3) are localized in caveolae of endothelial cells and play central roles in regulating blood pressure and flow, angiogenesis, and vascular inflammation [ 14 , 16 , 102 , 103 ].…”

“…In humans, it is well established that cadmium, lead, and mercury exposures increase serum cholesterol levels [ 12 ]. Correlations were also detected between blood concentrations of arsenic and mercury, and especially manganese and zinc, with alterations in the levels of plasmenyl phospholipids and sphingomyelin [ 160 ].…”

“…Environmental and occupational toxicants can bring about a great diversity of cellular and systemic alterations implicated in the short-term and long-term outcomes of toxic exposures [ 4 , 5 , 6 , 7 , 8 , 9 ]. The cellular effects of common pollutants (or their metabolites) can affect redox status, calcium homeostasis, metabolic and epigenetic programs, among other disturbances, but the key molecular targets and mechanisms of action of specific compounds remain unresolved [ 4 , 10 , 11 , 12 , 13 , 14 ].…”

Removal of Hydrophobic Organic Pollutants and Copper by Alginate-Based and Polycaprolactone Materials

“…Other pertinent players in environmental pollution are heavy metals which greatly impact the environment at the toxicological level [11]. These pollutants are common in water, and exposure to heavy metals and metalloids is associated with cancer and cardiovascular disorders [12,13].…”