Elsevier

Clinical Nutrition

Volume 24, Issue 1, February 2005, Pages 16-31
Clinical Nutrition

REVIEW
Dyslipidemia and inflammation: an evolutionary conserved mechanism

https://doi.org/10.1016/j.clnu.2004.08.004Get rights and content

Summary

Inflammation leads to changes in lipid metabolism aimed at decreasing the toxicity of a variety of harmful agents and tissue repair by redistributing nutrients to cells involved in host defence. Acute phase response, mediated by cytokines, preserves the host from acute injury. When this inflammation becomes chronic, it might lead to chronic disorders as atherosclerosis and the metabolic syndrome. The activation of the inflammatory cascade will induce a decrease in HDL-cholesterol (HDL-C), with impairment in reverse cholesterol transport, and parallel changes in apolipoproteins, enzymes, anti-oxidant capacity and ATP binding cassette A1-dependent efflux. This decrease in HDL-C and phospholipids could stimulate compensatory changes, as synthesis and accumulation of phospholipid-rich VLDL which binds bacterial products and other toxic substances, resulting in hypertriglyceridemia. The final consequence is an increased accumulation of cholesterol in cells.

When the compensatory response (inflammation) is not able to repair injury, it turns into a harmful reaction, and the lipid changes will become chronic, either by repeated or overwhelming stimulus, enhancing the formation of atherosclerotic lesions. Thus, the classical lipid changes associated with the metabolic syndrome (increased triglycerides and decreased HDL-C) may be envisioned as a highly conserved evolutionary response aimed at tissue repair. Under this assumption, the problem is not the response but the persistence of the stimulus.

Section snippets

Changes in HDL lipoprotein during inflammation

It is well known that HDL particles are fundamental for cholesterol reverse transport, and protect from coronary disease development.21 There are several mechanisms through which inflammation and cytokines can modify the size, composition and function of HDLs. During APR a wide range of changes in HDL apolipoprotein and enzymes occurs. These changes in HDL particles caused by inflammation not only reduce HDL-C levels but they also alter anti-oxidant properties of HDL and LDL protection from

Changes in VLDL lipoprotein and TGs during inflammation

Elevation of TG levels is considered as an independent cardiovascular risk factor, especially in the diabetic population.112, 113, 114 Nevertheless, it is difficult to establish an independent association between TGs and cardiovascular risk due to their close relation with HDL-C levels.115

Changes in LDL lipoprotein and cholesterol during inflammation

Most of the LDL particles are derived from the intravascular catabolism of VLDL. Catabolism of LDL occurs in both peripheral cells and the liver and is facilitated by both LDL-receptor- (LDL-R-) mediated and non-receptor-mediated pathways. Clinical and epidemiological studies have shown LDL-C as one of the most important cardiovascular risk factors.

Lipoprotein(a), inflammation and tissue repair

It has been hypothesized that Lp(a) could offered an evolutionary advantage to humans by promoting or accelerating the healing of wounds and the repair of tissue injuries and vascular lesions.199 In fact, Lp(a) behaves as an acute-phase reactant. The sequence of the apo(a) gene contains several IL-6-responsive elements that enhance transcription of the gene.200 IL-6 generates a marked, dose-dependent enhancement of apo(a) mRNA synthesis that leads to the accumulation of Lp(a) particles in

Conclusions

Lipoproteins can decrease the toxicity of a variety of harmful biological and chemical agents. Lipoproteins are directly involved in the host response to infection and tissue destruction. During acute illness, delivery of cholesterol to the liver for excretion is altered to allow cholesterol to remain in the tissues where it is needed for repair and regeneration of damaged membranes. In fact, lipoproteins have been found to be potent inhibitors of the infectivity of different viruses and to

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