{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:24:52Z","timestamp":1788326692494,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Black people bear a disproportionate burden of hypertension and hypertension-attributed chronic kidney disease. A role of apolipoprotein L1 (\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      ) risk variants (RVs; G1 and G2) in these conditions has been proposed, but genetic and observational studies have shown inconsistent results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Here, we investigated the causal role of\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      RVs using patient samples, transgenic animal models, and in vitro primary cellular experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      In the human kidney, APOL1 was highly expressed by glomerular podocytes and endothelial cells. Mice with podocyte-specific expression of the\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      RV (G2\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      ), but not those with the reference allele (G0), developed severe secondary hypertension after albuminuria and kidney disease. Mice expressing endothelium-specific G2\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      RVs developed mild hypertension with aging, which was exacerbated after unilateral nephrectomy and subsequent high-salt diet feeding. This condition was associated with a slight alteration in kidney function. In vitro and in vivo experiments demonstrated that the\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      RV activates the cytosolic nucleotide sensor STING (stimulator of interferon genes), leading to increased production of endothelin 1. Notably, mice with endothelium-specific STING knockout or those treated with an endothelin inhibitor showed protection from G2\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      RV\u2013mediated hypertension.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      These findings indicate a role of G2\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      in hypertension development through STING and endothelin 1 activation, offering new precision therapeutics for addressing hypertension in Black people carrying\n                      <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                      RVs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.124.071351","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T10:00:37Z","timestamp":1765447237000},"page":"396-414","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Cell-Specific Inducible Human\n                    <i>APOL1<\/i>\n                    Risk Variant Expression in Mice Causes Hypertension and Renal Damage"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8688-0695","authenticated-orcid":true,"given":"Fang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."},{"name":"Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China (F.L., X.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-7002","authenticated-orcid":true,"given":"Bibek","family":"Poudel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-0981","authenticated-orcid":true,"given":"Magaiver","family":"Andrade-Silva","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-2057","authenticated-orcid":true,"given":"Junnan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-4962","authenticated-orcid":true,"given":"Archana","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. Wahba, A.V., C.L., A.A., K.A.K., K.S.)."},{"name":"Penn-CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia (F.L., B.P., M.A.-S., J. Wu, A.R., J. 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