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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Cardiovascular Diseases*/genetics ; Cardiovascular Diseases*/therapy ; Heart Failure*/genetics ; Heart Failure*/therapy ; Hypertension*/genetics ; Hypertension*/therapy ; Atherosclerosis*/drug therapy ; Atherosclerosis*/genetics; Humans ; Aged ; Proprotein Convertase 9/genetics ; RNA, Small Interfering/genetics ; RNA, Small Interfering/therapeutic use ; RNA, Messenger

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.

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Keywords: amyloidosis; atherosclerosis; heart failure; hypertension; inclisiran; lepodisiran; olpasiran; patisiran; small interfering RNA; zilebesiran

EC 3.4.21.- (PCSK9 protein, human)
EC 3.4.21.- (Proprotein Convertase 9)
0 (RNA, Small Interfering)
0 (RNA, Messenger)

Date Created: 20240111 Date Completed: 20240112 Latest Revision: 20241019

20241019

PMC10778861

10.3390/ijms25010328

38203499