{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:33:38Z","timestamp":1790861618656,"version":"4.1.0"},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Atherosclerosis is a chronic inflammatory disease driven by macrophages. PKC\u025b (protein kinase C epsilon) is a serine\/threonine kinase involved in diverse cellular processes including migration, growth, differentiation, and survival. PKC\u025b acts in a context-dependent manner within the heart; however, its role in atherosclerosis is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Bone marrow\u2013derived macrophages from global PKC\u025b knockout mice were tested for lipid retention and cytokine secretion. Public gene set analysis assessed raw counts of PRKCE in human atheromas to determine translational relevance. A LysM Cre PKC\u025b\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      (myeloid-selective PKC\u025b knockout [m\u025bKO]) mouse was developed to study the impact of myeloid PKC\u025b on atherosclerosis. After confirming myeloid-selective PKC\u025b deletion, human-like hypercholesterolemia was induced, and multiple metrics of atherosclerosis were compared between wild-type (WT) and m\u025bKO plaques. RNA sequencing was used to provide unbiased insight into possible mechanisms by which PKC\u025b regulates atherosclerosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Public gene set analysis of human atherosclerotic plaque tissue revealed that PRKCE expression is inversely correlated with plaque vulnerability. Similarly, peritoneal macrophages from WT hypercholesterolemic mice have significantly lower PKC\u025b expression, providing a translational rationale for the generation of the m\u025bKO mouse. Quantitative polymerase chain reaction revealed no differences between genotypes in the expression of genes related to atherosclerosis, at either steady state or upon lipid loading, suggesting that loss of PKC\u025b does not fundamentally change the basal state and that differences seen are a result of a more complex pathway. Comparing descending aorta and aortic root plaques from WT and m\u025bKO hypercholesterolemic mice revealed that m\u025bKO plaques are larger, have larger foam cells and regions of necrosis, and thinner collagen caps. Upon lipid loading in vitro and in vivo, m\u025bKO macrophages retained significantly more cholesterol and lipid droplets than WT; Gene Ontology suggests higher expression of genes related to endocytosis in m\u025bKO macrophages compared with WT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>PRKCE expression is decreased in vulnerable human plaques and PKC\u025b decreases in mouse macrophages upon lipid loading. m\u025bKO plaques are larger and exhibit markers of vulnerability. With no differences in SR (scavenger receptor) expression, the impact of PKC\u025b deletion is more subtle than simple SR dysregulation. RNA sequencing implicates higher expression of genes involved in endocytosis, and m\u025bKO macrophages have significantly more lipid-containing endosomes. The data define the atherophenotype of m\u025bKO mice and demonstrate that PKC\u025b restricts lipid uptake into macrophages by a mechanism independent of SR expression. Taken together, these studies identify PKC\u025b as a novel atheroprotective gene, laying the foundation for mechanistic studies on the endocytic signaling networks responsible for the phenotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.125.323005","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T09:00:09Z","timestamp":1753347609000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of Myeloid Protein Kinase C Epsilon as a Novel Atheroprotective Gene"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1765-5948","authenticated-orcid":true,"given":"Alexis T.","family":"Wells","sequence":"first","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology (A.T.W., M.M.S., R.H.B., A.E.S., M.R.L.), Albany Medical College, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8536-2606","authenticated-orcid":true,"given":"Ramon","family":"Bossardi Ramos","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology (R.B.R.), Albany Medical College, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology (A.T.W., M.M.S., R.H.B., A.E.S., M.R.L.), Albany Medical College, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5463-8177","authenticated-orcid":true,"given":"Redwan H.","family":"Binrouf","sequence":"additional","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology (A.T.W., M.M.S., R.H.B., A.E.S., M.R.L.), Albany Medical College, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E.","family":"Swinegar","sequence":"additional","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology (A.T.W., M.M.S., R.H.B., A.E.S., M.R.L.), Albany Medical College, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-8805","authenticated-orcid":true,"given":"Michelle R.","family":"Lennartz","sequence":"additional","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology (A.T.W., M.M.S., R.H.B., A.E.S., M.R.L.), Albany Medical College, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","unstructured":"What is cardiovascular disease. 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