Lipid and Lipoprotein Basics

Understanding atherosclerosis necessitates knowledge of various lipids (especially sterols and fatty acids) and their homeostasis, including how they are synthesized, incorporated into and transported or trafficked within lipoproteins. Since atherogenesis is a lipoprotein mediated disease, it is essential to review their synthesis, structure (surface protein and lipid composition), catabolism, kinetics (how they interact with each other and the arterial wall) and ability to be influenced by other metabolites (such as glucose, reactive oxygen species, etc.). Understanding lipoproteins also requires a realization that there is a constant, continually on-going, dynamic, flow and remodeling of particles where lipid molecules and apoproteins are gained and lost and acquired through complex pathways involving catabolism (lipolysis) and interchange between particles. Simply stated, lipoproteins and their lipid content are in a continuous state of constant dynamic flux. This can be very underappreciated by looking at concentrations reported in a standard lipid panel. The more we understand this, the more we can begin to understand the etiology of atherogenesis and the far better we can understand how to influence lipoprotein pathobiology using lifestyle and pharmacological methods. Of prime importance is to know what laboratory tests best help us identify and properly diagnose lipoprotein structure, composition and kinetics and then relate those parameters to risk. There are many ways of assaying lipid and lipoprotein concentrations and characteristics: particle numbers, particle sizes, particle lipid content, particle apolipoprotein content, etc. Where the subject gets complex and where real world clinicians cannot go at this time is understanding the functionality of the lipoproteins (are they doing what they are supposed to be): exactly where do the particles lipidate, and where do the delipidate and do they have normal catabolism (lipolysis): is it the liver, the jejunum, some peripheral tissue, or the artery intima? Are the sterols, entering the artery or being eliminated as fecal sterols (cholesterol or bile acid)?