RESUMO
BACKGROUND: The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC). METHODS: Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, RESULTS: Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50â¯%, while non-cholinergic contractions were inhibited up to 80â¯% and 60â¯% for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75â¯%. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization. CONCLUSIONS: IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.
Assuntos
Proliferação de Células , Contração Muscular , Miócitos de Músculo Liso , Bexiga Urinária , Humanos , Contração Muscular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Suínos , Masculino , Talidomida/farmacologia , Talidomida/análogos & derivados , Músculo Liso/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Células Cultivadas , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lenalidomida/farmacologiaRESUMO
Fibro-adipose vascular anomaly (FAVA) is characterized by intramuscular vascular malformation with secondary overgrowth of further mesenchymal elements, particularly fibro-adipose tissue. A rare disease complicated by nonspecific, overlapping clinical and imaging features, FAVA is often misdiagnosed, causing a dilemma in its diagnostic and therapeutical management. We present a case of FAVA of the lower extremity.