L5 Research Center
Human plasma low-density lipoprotein (LDL) plays an important role in the risk of coronary artery disease (CAD). It is normally metabolized by liver and vascular cells via the LDL receptor (LDLR); however, genetic defects in LDLR expression or modifications to the LDL structure lead to plasma LDL accumulation and premature CAD as well as other atherosclerotic vascular abnormalities.
Evidence is now accumulating that some LDL particles carry a greater negative charge than the majority of LDL particles, which may be responsible for atherogenicity in dyslipidemia. These highly negatively charged LDL particles have been called “electronegative” LDL particles. These have been found to exhibit atherogenic properties in cultured vascular cells. Using anion-exchange chromatography to resolve human plasma LDL, we were able to separate LDL into 5 subfractions, with increasing negative surface charge from L1 to L5. Unlike the harmless L1 to L4, the exclusively atherogenic L5 is rejected by the normal LDLR, and is instead endocytosed into vascular endothelial cells through the lectin-like oxidized LDL receptor-1 (LOX-1). L5 is an extreme form of electronegative LDL and increases cardiac risks in subjects with hypercholesterolemia, type 2 diabetes mellitus, metabolic syndrome, and active smoking.
Establishment and History
Named after the 5th and final chromatographically resolved, charge-defined LDL subfraction, the L5 Research Center was established as one of the cross-Pacific research laboratories at CMUH in February 2010.
Led by Dr. Chu-Huang Chen (陳珠璜), Visiting Professor at CMU and Director of Vascular and Medicinal Research at Texas Heart Institute in Houston, Texas, USA, the center was established to fully characterize L5 and define its biological effects and clinical impacts.
To stay abreast of the most advanced technology and remain intellectually competitive at the international level, the center has constructed a collaborative network with established investigators from numerous institutions in Taiwan and abroad, including the Texas Heart Institute, Houston, Texas; Baylor College of Medicine, Houston, Texas; Cleveland Clinic and Case Western University, Cleveland, Ohio; and the National Cardiovascular Research Institute, Osaka, Japan.
Missions and Expertise
The L5 Research Center at CMUH in Taiwan and the Vascular and Medicinal Research Laboratory at Texas Heart Institute in Texas, USA share the same missions to collaboratively define new endogenous factors and mechanisms mediated by these factors for atherosclerosis, progenitor cell dysfunction, and vascular aging. This mission is based on our expertise in resolving different classes of lipoproteins into charge-defined subfractions. Starting from LDL, the scope of the research will expand to include other lipoprotein classes, in particular high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL).
The L5 Research Center at CMUH will examine the role of L5 in CAD by viewing the available human, in vivo, chemical and molecular, progenitor, and therapeutic evidence. Our goal is to be the first research facility to identify a naturally occurring lipoprotein factor directly responsible for atherosclerosis formation and CAD events.
On the basis of our preliminary data, we anticipate producing quality results in support of our hypothesis. Many state-of-the-art technologies will be employed, including the establishment of new mouse strains, cryo-electron microscopy, nanotechnology, in vivo monitoring of enzymatic activities, and a search for new herb and natural product combinations as new therapies for CAD.
With cutting-edge technologies and a wealth of talents, we hope to live up to the expectation of a “Team of Excellence” and lead the research in this novel and important field in the global research platform. Our ultimate goal is to guide the world’s research in atherosclerosis towards a new direction and form a solid basis for new, targeted, and effective treatment for this detrimental disease.