The atherogenic role of immune cells in familial hypercholesterolemia

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism that mainly occurs due to mutations in the low‐density lipoprotein receptor gene and is characterized by increased levels of low‐density lipoprotein cholesterol, leading to accelerated atherogenesis and premature coronary heart disease. Both innate and adaptive immune responses, which mainly include monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes, have been shown to play a key role for the initiation and progression of atherogenesis in the general population. In FH patients, these immune cells have been suggested to play specific pro‐atherosclerotic activities, from the initial leukocyte recruitment to plaque rupture. In fact, the accumulation of cholesterol crystals and oxLDL in the vessels in FH patients is particularly high, with consequent abnormal mobilization of immune cells and secretion of various pro‐inflammatory and chemokines. In addition, cholesterol accumulation in immune cells is exaggerated with chronic exposure to relevant pro‐atherosclerotic triggers. The topics considered in this review may provide a more specific focus on the immune system alterations in FH and open new insights toward immune cells as potential therapeutic targets in FH.

Long-term Prognosis after Treatment of Total Occluded Coronary Artery is well Predicted by Neutrophil to High-Density Lipoprotein Ratio: a Comparison Study

“…Neu / Lym was the second best survival predictor in our study (ROC AUC=688 and p<0.001, Kaplan-Meier p<0.001, multivariate survival analysis p=0.013). Neu has an acute role in plaque rupture as mentioned before, however, lymphocytes affect the plaque formation more chronically, depending on cholesterol concentrations [30]. In addition, Neu and HDL negatively affect the other's functions [31].…”

Increased extracellular vesicles (EVs) related to T cell-mediated inflammation and vascular function in familial hypercholesterolemia

“…[ 10 ]. High levels of lipids, such as cholesterol and triglycerides, directly activate both innate and adaptive immunity in all stages of atherogenesis [ 33 ], and it is widely known that different lymphocyte subsets play important roles in cellular and humoral immunity. In FH, immune cells play specific pro-atherosclerotic activities, from the initial leukocyte recruitment to the artery wall to plaque rupture/erosion, as reviewed in Ref.…”

“…In FH, immune cells play specific pro-atherosclerotic activities, from the initial leukocyte recruitment to the artery wall to plaque rupture/erosion, as reviewed in Ref. [ 33 ].…”

Mice lacking global Stap1 expression do not manifest hypercholesterolemia

“…This could be explained by the concentration of B-cells in the spleen and their presence in other organs, as the tissues were not perfused prior to collection. Some studies have associated STAP1 variations with cardiovascular disease [ 10 – 12 ], and immune cells have been linked with atherosclerosis and FH [ 32 ]. This study did not thoroughly investigate possible effects of STAP1 deletion on the immune system, but there were no obvious changes in B-cell subsets and IgG (data not shown).…”