Histone deacetylase inhibitors for cardiovascular conditions and healthy longevity

Autores da FMUP

• João Pedro Melo Marques Pinho Ferreira

  Autor

Participantes de fora da FMUP

• Pitt, B
• Zannad, F

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Histone deacetylase inhibitors (HDACi) regulate gene expression via epigenetic mechanisms. Accumulating evidence suggests that HDACi exert antiproliferative, antioxidant, antineoplastic, and proapoptotic effects through epigenetic mechanisms. Furthermore, HDACi also exert antithrombotic and antifibrotic effects through regulation of thrombotic and fibrotic transduction mechanisms. One of the oldest HDACi is valproic acid, which was first synthesised in 1882. After the discovery of its anticonvulsant properties for the treatment of epilepsy, the use of valproic acid was extended to other conditions, such as bipolar disorder and migraine. Given the accumulating evidence supporting the role of HDACi in the treatment of multiple medical conditions beyond epilepsy, the interest in novel potential indications for HDACi has been renewed. Considering the pleotropic epigenetic effects of HDACi, future studies could assess their efficacy and safety for cardiovascular disease prevention and treatment; treatment of venous thrombosis, Alzheimer's disease, autoimmune and proinflammatory conditions, chronic thromboembolic pulmonary hypertension, and pulmonary arterial hypertension; and as a coadjuvant therapy for cancer. Adequately designed and powered clinical trials are required to assess the efficacy and safety of HDACi before their clinical repurposing.

Keywords

• Antineoplastic Agents; Cardiovascular Diseases; Histone Deacetylase Inhibitors; Humans; Longevity; Valproic Acid; carbamazepine; givinostat; histone deacetylase inhibitor; hydralazine; mineralocorticoid receptor; phenobarbital; plasminogen activator inhibitor 1; tissue plasminogen activator; trichostatin A; urokinase; valproic acid; vorinostat; antineoplastic agent; histone deacetylase inhibitor; valproic acid; adriamycin-induced nephropathy; aging; Alzheimer disease; angiotensin II-induced cardiac hypertrophy; antiapoptotic activity; antifibrotic activity; antiinflammatory activity; antiproliferative activity; antithrombotic activity; apoptosis; atherosclerosis; atrial fibrillation; autoimmune disease; bipolar disorder; bleomycin-induced pulmonary fibrosis; cancer inhibition; cardiovascular disease; cerebral ischemia reperfusion injury; cerebrovascular accident; collagen-induced arthritis; degenerative disease; dementia; diabetes mellitus; diabetic nephropathy; diarrhea; diastolic dys