Lipids, Cholesterol, & Atherosclerosis - The Fernandez-Hernando Lab at Yale School of Medicine

Transcript

• 00:05Lipoproteins are small particles
• 00:07that are needed to transport lipids across the body
• 00:10and deliver these lipids to all the organs.
• 00:13But when these lipids are accumulated in blood stream in high levels,
• 00:16particularly the low density lipoproteins that carry a very large amount of cholesterol,
• 00:22they can be accumulated in wrong places like the arterial wall,
• 00:26and cause the initiation of formation of arthroscopic plaques.
• 00:31We also carry lipids in another good lipoproteins called high density lipoproteins.
• 00:37They have an opposite role and promote the uptake in lipids
• 00:41in the periphery, and retrieve these lipids back to the liver.
• 00:44Then this is the thing that we know is a good cholesterol that is thought
• 00:49to play an important role in protecting cardiovascular disease.
• 00:56My lab studies atherosclerosis
• 00:59which is a very complex disease that involved alteration in metabolism,
• 01:02being the accumulation of this bad cholesterol,
• 01:05LDL cholesterol in the arteries,
• 01:07the major factor that initiated the formation of these lesions.
• 01:11Then my lab is working in identifying novel
• 01:14molecular mechanisms that control lipoprotein metabolism,
• 01:17and in this regard, we discover a number of novel molecules
• 01:21called micro RNAs, playing an important role here.
• 01:24And also another set of molecules called angiopoietin lipoproteins.
• 01:28that control catabolism or recycling, of these lipoproteins in circulation.
• 01:33In top of that, we also are very interested in studying
• 01:37the chronic inflammatory response that occurs in the vessels where these lesions develop.
• 01:42Particularly interested in the role of these lipids
• 01:45modifying the innate immune responses that are important
• 01:49for the progression and the rupture of these lesions in the large arteries.
• 01:58We use models of living organisms that develop this disease,
• 02:01where we can study the initiation and progression of this pathology.
• 02:06We combine this with very basic vascular biology,
• 02:10cell biology, transcriptomics, single cell RNA sequencing,
• 02:14lipoprotein kinetics, lipoprotein fractionation, lipidomics,
• 02:18and also we collaborate with physican-sciencists to study
• 02:23the pathology also in human tissue as well.
• 02:29We know for the last two decades,
• 02:31that the statins has been very effective to protect against cardiovascular disease
• 02:34by significantly reducing the levels of LDL cholesterol.
• 02:39But still, there is a residual risk,
• 02:42and this is why we need a very specific mechanism
• 02:45that has to be very tightly regulated,
• 02:47that allow us to transport lipids to all the organs.
• 02:50But at the same time, have another good mechanism to rid out of cholesterol
• 02:55when we don't need more, then this is where the potential discovery
• 03:00of novel therapies that can protect attenuate the progression of disease.