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).