Have you ever seen the famous Monna Lisa by Leonardo Da Vinci? It is a misterious masterpiece. Have you ever thought that Monna Lisa could have 
been ill? If you look closely to the portrait you will note a light yellow stain near the nose, on the left eyelid. It is a xanthelasma. It is a kind of xanthoma, a deposition of yellowish cholesterol-rich material in tendons or other body parts.
THE STUDIES
In order to a Danish study xanthelasma palpebrarum can be considered a marker of atherosclerosis: 563 (4.4%) of participants had xanthelasmata and 3159 (24.8%) had arcus corneae at baseline. During the follow-up, 1872 developed myocardial infarction, 3699 developed ischaemic heart disease, 1498 developed ischaemic stroke, 1815 developed ischaemic cerebrovascular disease, and 8507 died. In all age groups in both women and men, absolute 10 year risk of myocardial infarction, ischaemic heart disease, and death increased in the presence of xanthelasmata.
Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study.2011
There are also other studies in which xanthelasmata are related to a lower level of HDL and an increased level of LDL. The apolipoproteins studied are ApoA1 and ApoB100. They are proteins that bind lipids to form lipoproteins and they are amphipathic, with a structure made of alpha-helices and beta-sheets.
ApoA1 belongs to HDL, the so called "good cholesterol", which transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary, and testes by both direct and indirect pathways. Instead ApoB100 is part of the LDL ("bad cholesterol") which can lead to the formation of foam cells and xanthomata. 
These LDL present modifications of their proteins and of their lipidic components, due to:
1. ROS ( Reactive Oxygen Species ): an oxydation lead fatty acids to aldehyds
2. Glycation due to an increased glycaemia
These modified LDL can enter the endothelial cells using scavenger receptors (different from the epatic ones) that are very important to remove extracellular toxic agents from the environment. These scavengers have the same pathway of the liver's ones but there is a lack in their regulation and they are always expressed on the cellular surface so they keep adsorbing esterified cholesterol. They can be transformed in MM LDL ( Minimal Modified ) and that means that they will not leave the subendothelial space any more. These MM LDL attract circulating monocytes which enter the endothelial cells too and adsorb esterified cholesterol becoming foam cells themselves. They also stimulate the expression of adhesion proteins that tie monocytes and let them pass from cell to cell in the subendothelium.
Xanthelasma palpebrarum: a marker of premature atherosclerosis (risk of atherosclerosis in xanthelasma).2012
Atheromata, which are strictly linked to xanthomata in order of their formation and structure, can lead to the formation of a thrombus ( the final product of the blood coagulation achieved via the aggregation of platelets ) which reduces the vessel lumen ( it can be associated with the formation of emboli and a heart attack too )
Low high-density lipoprotein cholesterol as the possible risk factor for stroke.2010
For an overview of the lipid metabolism look at lipid metabolism
CONCLUSION
Atherosclerosis is a very complex event and it takes years to develop and it needs several factors ( lipoproteins, modified LDL, enzymes such as COX et al., cytokines which are responsible of the inflammation too ), although the presence of xanthelasmata could be used in diagnosis as a non-invasive predictive factor for following complications.
In order to this studies we can suggest that Lisa Gherardini, the famous Gioconda, had a good chance of suffering of atherosclerosis.
Authors: Sara Pollano,Simone Reggio
