3.
Human pathologies and lipid abnormalities
| Disease | Membrane abnormality | Proposed molecular mechanisms |
|---|---|---|
| Cardiovascular (Hypertension) | Changes in membrane phospholipid and cholesterol levels, changes in fatty acid levels | Regulation of the membrane structure with concomitant alteration of membrane signalling, protein localization and activity |
| Cardiovascular (Sudden Cardiac death) | Changes in membrane levels of saturated and unsaturated fatty acids | Alterations in δ-6-desaturase activity in the coronary artery wall |
| Cardiovascular (Cardiac hypertrophy) | Changes in membrane levels of triacylglycerol species and other lipids | Changes in cell signalling and impaired triacylglycerol availability |
| Cancer (pathologic proliferation) | Changes in membrane fatty acid levels | Altered cell structure and function (including cell proliferation) |
| Cancer (multidrug resistance) | Alterations in the levels of phospholipid species (PS*) | Reduced drug intake and facilitated drug removal from cancer cells |
| Respiratory pathologies | Changes in the lipid composition of membrane microdomains | Alterations in mechanotransduction and other signalling processes |
| Renal Pathologies | Increased lipid peroxidation and augmented proportions of saturated fatty acids caused by haemodialysis | Increased cellular oxidative stress |
| Alzheimer's disease, Aging and neurodegeneration | Reduced levels of PUFA† in brain cell membranes | Altered expression of transthyretin and other genes related to learning, cognitive and integrative functions |
| Inflammation, autoimmune and related diseases | Release of pro-inflammatory lipids from membranes | Formation of eicosanoids from arachidonic acid, changes in membrane fluidity, changes in membrane lipid–protein interactions |
| Infectious diseases | Increased ceramide-enriched membrane domains | Modified membrane lipid domains act as platforms for a wide variety of virus, bacteria and parasite infections |
| Schizophrenia | Decreased proportion of PUFA† in membrane phospholipids | Myelin-related and neurotransmitter signalling dysfunctions |
| Obesity | Changes in membrane lipids | Alterations in membrane protein function |
| Alcohol-induced fetal damage | Changes in cell membrane composition | Various cell functions alterations |
| Coagulation (Scott Syndrome) | Defective PS* flip-flop translocation in membranes | Impaired interaction of coagulation factors and blood cell membranes |
| Triose Phosphate Isomerase deficiency | Lack of symptoms is associated with modification of membrane lipids and lipid fluidity | Changes in membrane protein–lipid interactions and in the activity of certain enzymes |
Adapted from [9].
*
PS, phosphatidylserine and †PUFA, polyunsaturated fatty acids.