Eryptosis and oxidative damage in hypertensive and dyslipidemic patients

Abstract

Arterial hypertension is a disease that often coexists with dyslipidemia. Both disorders can produce oxidative stress. Studies in vivo and in vitro have proven that oxidative stress can induce an increment of the erythrocyte apoptosis (eryptosis), through the rise of free intracellular calcium concentration ([Ca]). Higher levels of eryptosis have not been described in patients with hypertension, dyslipidemia, or both combined. This study involved 81 men between 26 and 50 years old, assorted into four groups: normotensive with and without dyslipidemia, and hypertensive with and without dyslipidemia. Hypertensive and/or dyslipidemic patients had double mean lipid peroxidation and 30% less mean GSH concentration than the normotensive non-dyslipidemic patients. Mean [Ca] in hypertensive patients was 100 and 200% higher, in patients without and with dyslipidemia, respectively, compared to normotensive patients. Dyslipidemic normotensive patients had three times higher mean PS externalization than the normotensive non-dyslipidemic patients, and the hypertension condition doubled this difference. Hypertensive patients had higher eryptosis associated with higher levels of [Ca] and oxidative stress, suggesting that eryptosis participates in the pathophysiological mechanisms of hypertension. The quantitative analysis, when the dyslipidemic factor is included, shows that oxidative stress-[Ca]-eryptosis do not follow a unique pattern in the different groups and suggests the existence of mechanisms of induction and molecular pathways alternative or additional to oxidative stress and [Ca], respectively.

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

“…Both arterial hypertension and dyslipidemia are known to generate oxidative stress. Accordingly, it was previously shown that hypertensive and/or dyslipidemic individuals had 30% lower GSH levels and a doubling of mean lipid peroxidation than normotensive patients without dyslipidemia (Fig. ).…”

“…). Taken together, these observations indicate that both hypertension and dyslipidemia, either alone or concomitantly, generate an increased amount of oxidative stress, although no additive effect of either condition has been observed . As oxidative stress is known to activate Ca 2+ permeable cation channels leading to Ca 2+ entry, hypertensive patients had a 100% and 200% higher mean [Ca 2+ ] i without and with dyslipidemia, respectively.…”

“…Hypertensive patients display higher erythrocyte lipid peroxidation than normotensive individuals and additionally show higher generation of superoxide ions, nitric oxide and hydrogen peroxide in leukocytes . Individuals with moderate, but untreated hypertension have a higher lipid peroxidation in erythrocytes than treated hypertensive or normotensive individuals . Furthermore, patients with hypertension were shown to have reduced activities of several erythrocyte enzymes including GPx, catalase and superoxide dismutase as well as lower GSH concentrations as compared to normotensive individuals (Fig.…”

Taurolidine Sensitivity of Eryptosis, the Suicidal Erythrocyte Death

“…Several inbitors of eryptosis have been identified [88][89][90][91]. Eryptosis is enhanced in several clinical conditions including iron deficiency [33], dehydration [33], hyperphosphatemia [33], vitamin D excess [33], chronic kidney disease (CKD) [92][93][94][95][96][97], hemolytic-uremic syndrome [98], autoimmune hemolytic anemia [99], diabetes [33], hypertension and dyslipidemia [100], hepatic failure [101], malignancy [102][103][104], arteritis [105], systemic lupus erythematosus [106], sepsis [107,108], malaria [33,109,110], sickle-cell disease [33], beta-thalassemia [33], Hb-C and G6PD-deficiency [33], Wilsons disease [107], as well as advanced age [33]. Eryptosis is fostered by storage for transfusion [41,42,58,111].…”

Stimulation of Eryptosis by Afatinib

“…Several substances inhibit eryptosis [113][114][115][116]. Enhanced eryptosis is observed in diverse clinical conditions including iron deficiency [58], vitamin D excess [117], chronic kidney disease (CKD) [118][119][120][121][122][123], hemolytic-uremic syndrome [124], autoimmune hemolytic anemia [125], diabetes [126], hypertension and dyslipidemia [127], hepatic failure [128], malignancy [129][130][131], arteritis [132], systemic lupus erythematosus [133], sepsis [134,135], malaria [58,136,137], sicklecell disease [58], beta-thalassemia [58], Hb-C and G6PD-deficiency [58], Wilsons disease [134], as well as advanced age [138]. Eryptosis further increases following storage for transfusion [67,68,83,139] and is enhanced in erythrocytes from newborns exposed to oxidative stress [58,140].…”