Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension

• Published in: International Journal of Molecular Sciences Vol. 25; no. 1; p. 328
• Main Authors: Sarzani, Riccardo, Spannella, Francesco, Di Pentima, Chiara, Giulietti, Federico, Landolfo, Matteo, Allevi, Massimiliano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.12.2023; MDPI
• Subjects: Aged; Amyloidosis; Angiotensin; Antihypertensive drugs; Apolipoproteins; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - genetics; Cardiovascular disease; Cardiovascular Diseases - genetics; Cardiovascular Diseases - therapy; Cholesterol; Clinical medicine; Disease; Drug dosages; Health aspects; Heart failure; Heart Failure - genetics; Heart Failure - therapy; Humans; Hypertension; Hypertension - genetics; Hypertension - therapy; Lipoprotein A; Lipoproteins; Liver; Low density lipoproteins; Patients; Proprotein Convertase 9 - genetics; Proteins; Review; RNA, Messenger; RNA, Small Interfering - genetics; RNA, Small Interfering - therapeutic use; atherosclerosis; heart failure; inclisiran; amyloidosis; lepodisiran; olpasiran; small interfering RNA; zilebesiran; patisiran; hypertension
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25010328

Small interfering RNA (siRNA) represents a novel, fascinating therapeutic strategy that allows for selective reduction in the production of a specific protein through RNA interference. 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.