PARP1 and cardiovascular disorders (stroke)
Accumulating evidences have reported PARP activation in oxidative stress related pathologies including cardiovascular disorders and stroke. Role of PARP1 in regulating the pathological stress in cardiovascular disease can be predicted by its interaction with Kruppel like factor 5 (KLF5) transcription factor (Suzuki et al., 2007). HYDAMTIQ, a PARP1 inhibitor has been illustrated to confer neuroprotection post stroke (Moroni et al., 2012). The reason for morbidity in multiple sclerosis, trauma and stroke is dysfunction of blood brain barrier and subsequently leukocyte infiltration and neuro-inflammation. Recent evidences have suggested PARP inhibition diminishes inflammation in leukocytes via attenuation of adhesion and migration (Rom et al., 2016).
The only approved treatment for thrombolysis in ischemic stroke is recombinant tissue plasminogen activator (rtPA), but at certain dose and in some conditions, it can aggravate the risk of haemorrhage. rtPA is reported to increase PARP1 activity and inhibition of PARP1 prevents the vascular toxicity of rtPA on brain (Teng et al., 2013). Thus, co-treatment of PARP inhibitor with rtPA seems to be a promising approach for handling thrombolysis effects. PARP1 inhibition has been shown to suppress inflammation-related plaque formation, another reason for ischemia (von Lukowicz et al., 2008).