1.The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells.
Ruiz-Magaña MJ1, Martínez-Aguilar R1, Lucendo E1, Campillo-Davo D1, Schulze-Osthoff K2,3, Ruiz-Ruiz C1,4. Oncotarget. 2016 Mar 3. doi: 10.18632/oncotarget.7871. [Epub ahead of print]
Epigenetic therapies have emerged as promising anticancer approaches, since epigenetic modifications play a major role in tumor initiation and progression. Hydralazine, an approved vasodilator and antihypertensive drug, has been recently shown to act as a DNA methylation inhibitor. Even though hydralazine is already tested in clinical cancer trials, its mechanism of antitumor action remains undefined. Here, we show that hydralazine induced caspase-dependent apoptotic cell death in human p53-mutant leukemic T cells. Moreover, we demonstrate that hydralazine triggered the mitochondrial pathway of apoptosis by inducing Bak activation and loss of the mitochondrial membrane potential. Hydralazine treatment further resulted in the accumulation of reactive oxygen species, whereas a superoxide dismutase mimetic inhibited hydralazine-induced cell death. Interestingly, caspase-9-deficient Jurkat cells or Bcl-2- and Bcl-xL-overexpressing cells were strongly resistant to hydralazine treatment, thereby demonstrating the dependence of hydralazine-induced apoptosis on the mitochondrial death pathway.
2.Risks of parenteral antihypertensive therapy for the treatment of severe maternal hypertension are low.
Sharma KJ1, Rodriguez M1, Kilpatrick SJ1, Greene N1, Aghajanian P1. Hypertens Pregnancy. 2016 Feb;35(1):123-8. doi: 10.3109/10641955.2015.1117098. Epub 2016 Feb 24.
OBJECTIVE: To determine whether the incidence of hypotension or adverse fetal heart tracing (FHT) category change differed following antepartum administration of intravenous (IV) labetalol versus hydralazine.
3.Heart Failure Update: Outpatient Management.
Wojnowich K1, Korabathina R2. FP Essent. 2016 Mar;442:18-25.
Outpatient management of heart failure (HF) is aimed at treating symptoms and preventing hospitalizations and readmissions. Management is initiated in a stepwise approach. Blockade of the renin-angiotensin system is a cornerstone of therapy and should be started, along with beta blockers, as soon as the diagnosis of HF is made. Other drugs, including diuretics, aldosterone antagonists, hydralazine, and nitrates, may be added based on symptoms and American College of Cardiology/American Heart Association stage. Despite a great interest in and theoretical benefit of naturoceutical products in the mitigation of oxidative stress and HF progression, none has been proven to be beneficial, and concerns exist regarding their interactions with standard HF drugs. Other nonpharmacologic interventions, including sodium restriction, regular exercise, and/or cardiac rehabilitation, should be initiated at diagnosis. HF often is progressive, and clinicians should be aware of late stage management options, including implantable devices, cardiac transplantation, and hospice care.
4.Novel epigenetic-based therapies useful in cardiovascular medicine.
Napoli C1, Grimaldi V1, De Pascale MR1, Sommese L1, Infante T1, Soricelli A1. World J Cardiol. 2016 Feb 26;8(2):211-9. doi: 10.4330/wjc.v8.i2.211.
Epigenetic modifications include DNA methylation, histone modifications, and microRNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of CpG islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression (e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of microRNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense microRNAs could offer better therapeutic benefits in clinical practice.