rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2024-3018JQXOBWrpcardio-3018Research ArticleCURRENT QUESTIONS OF CLINICAL PHARMACOLOGYАКТУАЛЬНЫЕ ВОПРОСЫ КЛИНИЧЕСКОЙ ФАРМАКОЛОГИИNLRP3 Inflammasome — a new universal target of asymptomatic hyperuricemia and gout managementИнфламмасома NLRP3 — новая универсальная мишень терапевтического воздействия у пациентов с бессимптомной гиперурикемией и подагройhttps://orcid.org/0000-0003-3501-2354ЛебедевП. А.LebedevP. A.

Лебедев Петр Алексеевич.

Самара

Petr A. Lebedev.

Samara

palebedev@yahoo.comhttps://orcid.org/0000-0002-8510-3118ВоловаЛ. Т.VolovaL. T.

Волова Лариса Теодоровна.

Самара

Larisa T. Volova.

Samara

l.t.volova@samsmu.ruhttps://orcid.org/0000-0002-0444-8174ОсинаН. К.OsinaN. K.

Осина Наталья Константиновна.

Самара

Natalia K. Osina.

Samara

n.k.osina@samsmu.ruhttps://orcid.org/0000-0001-7021-4061ПаранинаЕ. В.ParaninaE. V.

Паранина Елена Владимировна.

Самара

Elena V. Paranina.

Samara

eles77@list.ruСамарский государственный медицинский университет Минздрава РоссииРоссияSamara State Medical UniversityRussian Federation202419062024203331339Copyright © Lebedev P.A., Volova L.T., Osina N.K., Paranina E.V., 20242024Лебедев П.А., Волова Л.Т., Осина Н.К., Паранина Е.В.Lebedev P.A., Volova L.T., Osina N.K., Paranina E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/3018

From modern perspective, hyperuricemia should be considered as a trigger of inflammatory activity in tissues and organs, leading to the formation of tophi, arthropathy, kidneys and cardiovascular system damage. Similarly, hypercholesterolemia, a proven factor in atherogenesis-far from all patients leads to the development of relevant clinical events. This commonality may be explained by the involvement of universal inflammatory mechanism. The key mediator of gout attacks is recognized as IL-1β, a product of NLRP3 (NLR family pyrin domain containing 3) inflammasome activation (complex multiprotein), responsible for local inflammatory response in synovial membrane and periarticular tissues with participation of macrophages and neutrophils. NLRP3 inflammasome activation is carried out by uric acid crystals, cholesterol exclusively after priming by lipopolysaccharides, peroxidation products and other damage factors associated with aging and comorbid conditions typical for gout and cardiovascular diseases. In addition, NLRP3 inflammasome activity is genetically determined and determines the frequency of these conditions. The discussed mechanism explains why the impact on factors associated with comorbidity is able to reduce the frequency of gout attacks along with cardiovascular outcomes. New clinically relevant pleotorpic effects of statins, sodium-glucose cotransporter-2 inhibitors, which have advantages over urates-lowering therapy in patients with asymptomatic hyperuricemia and can modify the course of gout, are demonstrated. Their anti-inflammatory properties, cardio and renoprotective effects, and tolerability advantages are emphasized. Blocking the activity of inflammasome is considered as a new universal therapeutic target for rheumatology and cardiology.

С современных позиций гиперурикемию (ГУ) следует рассматривать как триггер воспалительной активности в тканях и органах, приводящей к формированию тофусов, артропатии, поражению почек и сердечно-сосудистой системы. Однако у подавляющего большинства пациентов с длительной ГУ подагра никогда не развивается. Точно также, гиперхолестеринемия, доказанный фактор атерогенеза, далеко не у всех пациентов приводит к развитию соответствующих клинических событий. Это общность может быть объяснена вовлечением универсального механизма воспаления. Ключевым медиатором острых приступов подагры признан интерлейкин (IL)-1β, продукт активации инфламмасомы NLRP3 (NLR family pyrin domain containing 3), сложного мультипротеинового комплекса, ответственный за местную воспалительную реакцию в синовиальной оболочке и периартикулярных тканях с участием макрофагов и нейтрофилов. Активация инфламмасомы NLRP3 осуществляется кристаллами мочевой кислоты (МК), холестерина исключительно после прайминга липополисахаридами, продуктами перекисного окисления и другими факторами повреждения, ассоциированными со старением и коморбидными состояниями, типичными для подагры и сердечно-сосудистых заболеваний. К тому же активность инфламмасомы NLRP3 генетически детерминирована и определяет частоту этих состояний. Обсуждаемый механизм объясняет, почему воздействие на факторы, связанные с коморбидностью, способно снизить частоту приступов подагры наряду с сердечно-сосудистыми исходами. В статье показаны новые клинически значимые плейотропные эффекты статинов и ингибиторов натрий-глюкозного транспортера 2 типа, которые имеют преимущества перед уратснижающей терапией у пациентов с бессимптомной ГУ и способны модифицировать течение подагры. Подчеркиваются их противовоспалительные свой­ства, кардио- и ренопротективные эффекты, пре­имущества в переносимости. Блокирование активности инфламмасомы рассматривается как новая универсальная для ревматологии и кардиологии терапевтическая мишень, особенно при состояниях повышенного сердечно-сосудистого риска, ассоциированного с ГУ.

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The authors declare that there are no conflicts of interest present.