{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:45:22Z","timestamp":1782992722552,"version":"3.54.5"},"reference-count":68,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Caldesmon is an actomyosin\u2010tropomyosin\u2013binding protein with pleiotropic functions that generally acts as an inhibitor of actomyosin\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">ATPase<\/jats:styled-content>\n                      activity. This study aims to explore the role of\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      in regulation of preglomerular vascular tone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Expression of\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      , myosin light chain, and \u03b1\u2010smooth muscle actin was assessed by western blot of interlobar arteries (IAs) from young and old mice or human renal arteries from patients who underwent nephrectomy or tumor enucleation.\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs<\/jats:styled-content>\n                      were obtained from wild\u2010type or heterozygous mice, carrying a mutant allele that ablates both\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      isoforms (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      ). In\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs<\/jats:styled-content>\n                      , the vasoreactivity to \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010agonist phenylephrine, the soluble guanylate cyclase activator cinaciguat, and inhibitors of\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">RhoA<\/jats:styled-content>\n                      \u2010associated protein kinase\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">Y27632<\/jats:styled-content>\n                      or p21\u2010activated protein kinase 1\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IPA\u20103<\/jats:styled-content>\n                      were tested by wire myography.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Caldesmon was expressed in all preglomerular vessels of mice and humans. In\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs of young mice<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      protein was 50% less than in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs<\/jats:styled-content>\n                      of wild\u2010type\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">mice<\/jats:styled-content>\n                      . In\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs of old mice<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      was less than in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs of young mice<\/jats:styled-content>\n                      and not significantly different between\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      and wild\u2010type.\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">Caldesmon<\/jats:styled-content>\n                      mutation did not affect phenylephrine\u2010induced contraction or cinaciguat sensitivity but induced a rightward shift of\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">Y27632<\/jats:styled-content>\n                      \u2010induced relaxation in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs of young and old mice<\/jats:styled-content>\n                      and a reduction in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IPA\u20103\u2013<\/jats:styled-content>\n                      induced relaxation by 50% only in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">IAs of young mice<\/jats:styled-content>\n                      . In human renal arteries,\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      expression negatively correlated with age and the presence of renal inflammation. In the inflammation group, a reduction in estimated glomerular filtration rate was detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This study provides cumulative evidence that caldesmon is a marker of age and inflammation\u2010related changes in preglomerular vascular function. Our work supports the view that in the renal vasculature,\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">caldesmon<\/jats:styled-content>\n                      expression is age dependent and determines its sensitivity to the\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">RhoA<\/jats:styled-content>\n                      \u2010associated protein kinase\/p21\u2010activated protein kinase\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">1<\/jats:styled-content>\n                      regulatory pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046679","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:03:26Z","timestamp":1768827806000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Vascular Tone of Preglomerular Renal 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