{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:50:46Z","timestamp":1785750646028,"version":"3.56.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The pathophysiology of familial thoracic aortic aneurysm and dissection (TAAD) is linked to genetic variants that affect aortic components. Although hypertension is a risk factor for TAAD, the precise genetic link remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>A family with autosomal dominant TAAD complicated by hypertension was studied to identify candidate mutations. The effect of the identified mutation on TAAD development was investigated using a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9\u2013generated knock-in mouse model to elucidate the mechanism underlying hypertension-induced TAAD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The\n              <jats:italic>KCNJ5<\/jats:italic>\n              p.R242Q mutation was identified in the family and met the criteria for cosegregation, rarity, and conservation. Utilizing our mouse model, we observed that a significant proportion of heterozygous mice with the mutation displayed dilated thoracic aortas. The mutation\u2019s allele dose was positively correlated with TAAD incidence following \u03b2-aminopropionitrile monofumarate treatment. Pathological changes in the thoracic aorta, including collagen deposition and dilation, elevated transforming growth factor-\u03b2 activity, and extracellular matrix remodeling, were associated with hypertension. Furthermore, the mutation was found to induce lifelong isolated systolic hypertension, attributable to autonomous epinephrine secretion from the adrenal medulla. Unlike wild-type, mutated\n              <jats:italic>KCNJ5<\/jats:italic>\n              was highly expressed in the adrenal medulla instead of the adrenal cortex. Treatment with the adrenergic \u03b2\u2013receptor blocker propranolol reduced systolic hypertension and mitigated TAAD in the heterozygous mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              Familial TAAD may stem from\n              <jats:italic>KCNJ5<\/jats:italic>\n              dysfunction in the G-protein\u2013coupling domain, causing isolated systolic hypertension via increased epinephrine secretion and disruption of thoracic aortic homeostasis. These findings establish a genetic link between systolic hypertension and TAAD.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.23795","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T10:00:24Z","timestamp":1738749624000},"page":"752-764","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Autonomous Epinephrine Release by KCNJ5 Mutation Drives Familial Thoracic Aortic Aneurysm and Dissection"],"prefix":"10.1161","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6603-3508","authenticated-orcid":true,"given":"Yanyu","family":"Duan","sequence":"first","affiliation":[{"name":"Engineering Research Center of Intelligent Acoustic Signals of Jiangxi Province, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education (Y.D., C.W., N.H., Z. Liu), Gannan Medical University, Ganzhou, China."},{"name":"Ganzhou Cardiovascular Rare Disease Diagnosis and Treatment Technology Innovation Center (Y.D., Z. Liu), Gannan Medical University, Ganzhou, China."},{"name":"Heart Medical Centre (Y.D., Z. Lai, Q.Y., Z. Liu), First Affiliated Hospital of Gannan Medical University, Ganzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Wu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Intelligent Acoustic Signals of Jiangxi Province, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education (Y.D., C.W., N.H., Z. Liu), Gannan Medical University, Ganzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghong","family":"Lai","sequence":"additional","affiliation":[{"name":"Heart Medical Centre (Y.D., Z. Lai, Q.Y., Z. Liu), First Affiliated Hospital of Gannan Medical University, Ganzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3659-2418","authenticated-orcid":true,"given":"Qunxing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Heart Medical Centre (Y.D., Z. Lai, Q.Y., Z. Liu), First Affiliated Hospital of Gannan Medical University, Ganzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naixing","family":"Hu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Intelligent Acoustic Signals of Jiangxi Province, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education (Y.D., C.W., N.H., Z. 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