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In the cardiovascular (CV) field, several siRNAs have been developed in the last decade. Inclisiran has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) circulating levels with a reassuring safety profile, also in older patients, by hampering proprotein convertase subtilisin\/kexin type 9 (PCSK9) production. Olpasiran, directed against apolipoprotein(a) mRNA, prevents the assembly of lipoprotein(a) [Lp(a)] particles, a lipoprotein linked to an increased risk of ischemic CV disease and heart valve damage. Patisiran, binding transthyretin (TTR) mRNA, has demonstrated an ability to improve heart failure and polyneuropathy in patients with TTR amyloidosis, even in older patients with wild-type form. Zilebesiran, designed to reduce angiotensinogen secretion, significantly decreases systolic and diastolic blood pressure (BP). Thanks to their effectiveness, safety, and tolerability profile, and with a very low number of administrations in a year, thus overcoming adherence issues, these novel drugs are the leaders of a new era in molecular therapies for CV diseases.<\/jats:p>","DOI":"10.3390\/ijms25010328","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T04:40:44Z","timestamp":1703565644000},"page":"328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5159-0181","authenticated-orcid":false,"given":"Riccardo","family":"Sarzani","sequence":"first","affiliation":[{"name":"Internal Medicine and Geriatrics, ESH \u201cHypertension Excellence Centre\u201d, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy"},{"name":"Department of Clinical and Molecular Sciences, University \u201cPolitecnica delle Marche\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-7819","authenticated-orcid":false,"given":"Francesco","family":"Spannella","sequence":"additional","affiliation":[{"name":"Internal Medicine and Geriatrics, ESH \u201cHypertension Excellence Centre\u201d, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy"},{"name":"Department of Clinical and Molecular Sciences, University \u201cPolitecnica delle Marche\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Di Pentima","sequence":"additional","affiliation":[{"name":"Internal Medicine and Geriatrics, ESH \u201cHypertension Excellence Centre\u201d, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Giulietti","sequence":"additional","affiliation":[{"name":"Internal Medicine and Geriatrics, ESH \u201cHypertension Excellence Centre\u201d, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Landolfo","sequence":"additional","affiliation":[{"name":"Internal Medicine and Geriatrics, ESH \u201cHypertension Excellence Centre\u201d, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy"},{"name":"Department of Clinical and Molecular Sciences, University \u201cPolitecnica delle Marche\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Allevi","sequence":"additional","affiliation":[{"name":"Internal Medicine and Geriatrics, ESH \u201cHypertension Excellence Centre\u201d, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy"},{"name":"Department of Clinical and Molecular Sciences, University \u201cPolitecnica delle Marche\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1056\/NEJMcibr1613559","article-title":"Targeting Therapeutic Oligonucleotides","volume":"376","author":"Levin","year":"2017","journal-title":"N. 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