Lina Badimon1, Teresa Padró, Judit Cubedo. 1. aCardiovascular Science Institute - ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau) and CiberCV bCardiovascular Research Chair UAB, Barcelona, Spain.
Abstract
PURPOSE OF REVIEW: Familial hypercholesterolemia, represents one of the most extreme clinical entities associated with premature coronary artery disease (CAD). However, clinical manifestation of CAD varies across cohorts and individual patients suggesting the existence of additional non-LDL factors potentially contributing to their cardiovascular burden. RECENT FINDINGS: Changes in HDL-associated proteins appear as one of the potential additional factors contributing to the cardiovascular risk in familial hypercholesterolemia. Specifically, the content of Apo M-SP1 in HDL3 has been directly associated with cholesterol efflux capacity. In addition, a coordinated decrease in the content of Apo L1 and LCAT in HDL3 has been related to the presence of corneal arcus and to bad prognosis in familial hypercholesterolemia patients after an acute ischemic event. In fact, HDL3 particles of familial hypercholesterolemia patients have diminished antioxidant and anti-inflammatory function. SUMMARY: The identification of the specific changes in HDL-associated proteins that contribute to the increased cardiovascular risk of familial hypercholesterolemia patients could be useful for the development of novel therapeutic targets. These novel strategies, in combination with current lipid-lowering therapies, may help to reduce the residual risk found in these patients.
PURPOSE OF REVIEW: Familial hypercholesterolemia, represents one of the most extreme clinical entities associated with premature coronary artery disease (CAD). However, clinical manifestation of CAD varies across cohorts and individual patients suggesting the existence of additional non-LDL factors potentially contributing to their cardiovascular burden. RECENT FINDINGS: Changes in HDL-associated proteins appear as one of the potential additional factors contributing to the cardiovascular risk in familial hypercholesterolemia. Specifically, the content of Apo M-SP1 in HDL3 has been directly associated with cholesterol efflux capacity. In addition, a coordinated decrease in the content of Apo L1 and LCAT in HDL3 has been related to the presence of corneal arcus and to bad prognosis in familial hypercholesterolemiapatients after an acute ischemic event. In fact, HDL3 particles of familial hypercholesterolemiapatients have diminished antioxidant and anti-inflammatory function. SUMMARY: The identification of the specific changes in HDL-associated proteins that contribute to the increased cardiovascular risk of familial hypercholesterolemiapatients could be useful for the development of novel therapeutic targets. These novel strategies, in combination with current lipid-lowering therapies, may help to reduce the residual risk found in these patients.
Authors: Nicholas J Woudberg; Sarah Pedretti; Sandrine Lecour; Rainer Schulz; Nicolas Vuilleumier; Richard W James; Miguel A Frias Journal: Front Pharmacol Date: 2018-01-22 Impact factor: 5.810