{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:01:51Z","timestamp":1793282511912,"version":"4.5.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Familial hypercholesterolemia (FH) is the most common inborn metabolic disease, characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased risk for premature cardiovascular disease (CVD). Non-coding RNAs (ncRNAs) are promising biomarkers in CVD, but their role in pediatric FH remains unclear. We investigated circulating ncRNAs in pediatric heterozygous FH (heFH), focusing on lipid-lowering regimens and cardiovascular risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifty-one heFH patients and 17 controls (age 5\u201319 years) were prospectively enrolled and fasting serum and clinical data, including carotid intima-media thickness (cIMT) and echocardiography, collected. Small RNA sequencing was followed by targeted qPCR validation of candidate ncRNAs. Subgroup analyses compared newly diagnosed, diet-treated, and pharmacological lipid-lowering therapy (LLT)-obtaining patients. Additionally, miRNAs formerly described as atherosclerosis-associated were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MiR-182-5p (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012) and hsa-piR-28004 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.024) were significantly downregulated in newly diagnosed heFH patients vs. controls. MiR-122-5p was significantly upregulated in patients under LLT compared to both newly diagnosed patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037) and controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013). Hsa-piR-28004 expression levels correlated with oxidized LDL (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\n                      <jats:italic>0.345, p<\/jats:italic>\n                      \u2009=\u2009\n                      <jats:italic>0.005<\/jats:italic>\n                      ), HDL-C (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.282;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.023) and cIMT (\n                      <jats:italic>r\u2009\u2248\u2009<\/jats:italic>\n                      \u22120.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009\n                      <jats:italic>&lt;\u2009<\/jats:italic>\n                      0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MiR-182-5p and hsa-piR-28004 may serve as early indicators of disease, independent of traditional risk factors. Upregulation of miR-122-5p under LLT suggests involvement in treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This is the first comprehensive profiling of both microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) in children and adolescents with heterozygous familial hypercholesterolemia (heFH).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Circulating miR-182-5p, miR-122-5p and hsa-piR-28004 are potential early indicators of disease and treatment response in pediatric heFH.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MiRNAs identified to be associated with atherosclerosis in adults are not robustly expressed in pediatric heFH, underscoring age-specific molecular differences.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings support the potential of non-coding RNAs (ncRNAs) as non-invasive biomarkers for improved diagnosis, monitoring, and personalized risk assessment in children and adolescents with heFH beyond traditional lipid metrics.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-04894-9","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:53:08Z","timestamp":1773334388000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MiR-182-5p, miR-122-5p and hsa-piR-28004 as indicators of disease and treatment in pediatric familial hypercholesterolemia"],"prefix":"10.1038","author":[{"given":"Katharina Sophia","family":"Mair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Baumgartner-Kaut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Lischka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Nigmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Neyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schanzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gradwohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiana-Aura","family":"Giurgea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerfried","family":"Pesau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Willfort-Ehringer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Heno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Michel-Behnke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Greber-Platzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Zeyda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"4894_CR1","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1093\/eurheartj\/ehv157","volume":"36","author":"A Wiegman","year":"2015","unstructured":"Wiegman, A. et al. 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