The Role of Necroptosis in Atherosclerotic Disease

It is now known that cells do not always die by apoptosis, but can also undergo a process known as programmed cell necrosis, or necroptosis. In a study recently published in Science Advances, investigators reported that this proinflammatory process is active in human atherosclerosis, may promote growth of the necrotic core, and may serve as a novel molecular imaging and translational therapeutic target. These findings represent a major step in our goal to reduce coronary disease and stroke

Genome-Wide Association Studies Candidate Gene to Dual Modifier of Nonalcoholic Steatohepatitis and Atherosclerosis

Nonalcoholic steatohepatitis is a common disease involving chronic accumulation of fat and inflammation in the liver, often leading to advanced fibrosis, cirrhosis, and cancer. It is known that nonalcoholic steatohepatitis shares many features with atherosclerosis; however, there are still no effective therapeutics. In a recent study published in Nature, investigators demonstrated that mice lacking a high-density lipoprotein–associated gene were surprisingly protected from both steatohepatitis and atherosclerosis through the stabilization of the liver X receptor. This work reveals a timely candidate target for 2 highly prevalent cardiovascular diseases

High-Density Lipoprotein Nanoparticle Imaging in Atherosclerotic Vascular Disease

Summary: Nanoparticles promise to advance the field of cardiovascular theranostics. However, their sustained and targeted delivery remains an important obstacle. The body synthesizes some ânaturalâ nanoparticles, including high-density lipoprotein (HDL), which may home to the atherosclerotic plaque and promote cholesterol efflux. In a recent article published in JACC: Cardiovascular Imaging, investigators generated modified, radiolabeled HDL nanoparticles and confirmed they accumulated in atherosclerotic lesions from several different species. These approaches hold promise for the noninvasive diagnosis of vulnerable plaque and in the stratification of patients in whom HDL-mimetic therapy may have a clinical benefit. Key Words: atherosclerosis, HDL, imaging, nanoparticles, macrophages/monocyte

The Intersection of Genome-Wide Association Studies and High-Throughput Small Interfering Ribonucleic Acid Screens Allows for the Identification of Novel Pathways Relevant to Atherosclerosis

Summary: It is now known that the internalization and transcytosis of low density lipoprotein (LDL) in the vessel wall occurs through molecular pathways independent of the LDL receptor. In a study recently published in Nature Communications, investigators cross-referenced results from a genome-wide ribonucleic acid interference screen with targets identified in publicly-available genome-wide association studies datasets to identify activin-like kinase 1 as a novel driver of this process. This approach has relevance to the field of atherosclerosis, and could be used as a model for the prioritization of future âhitsâ in large-scale genomic screens. Key Words: activin-like kinase 1, atherosclerosis, endothelial cells, genome-wide association studies, genome-wide RNAi scree

The Promise and Challenge of Induced Pluripotent Stem Cells for Cardiovascular Applications

The recent discovery of human-induced pluripotent stem cells (iPSC) has revolutionized the field of stem cells. iPSC have demonstrated that biological development is not an irreversible process and that mature adult somatic cells can be induced to become pluripotent. This breakthrough is projected to advance our current understanding of many disease processes and revolutionize the approach to effective therapeutics. Despite the great promise of iPSC, many translational challenges still remain. The authors review the basic concept of induction of pluripotency as a novel approach to understand cardiac regeneration, cardiovascular disease modeling, and drug discovery. They critically reflect on the current results of pre-clinical and clinical studies using iPSC for these applications with appropriate emphasis on the challenges facing clinical translation