Targeting inducible Nitric Oxide Synthase (iNOS) in the prevention of vascular damage and cardiac inflammation in CVD

Nafees Uddin Chowdhury^a, Abida Tisha^b, Juthika Sarker^b, Pulak Dev Nath^b, Nowshin Ahmed^b, Shahanshah Abdullah^b, Tasdik Farooq^b, Waich Mahmud^b, Md. Mohabbulla Mohib^b,c, Md. Abu Taher Sagor^b

The molecular mechanism of iNOS that leads to CVD is comprehensively summarized in this review so as to aid in drug discovery strategies for the treatment of CVD.

Abstract

Vascular damage and subsequent cardiac failure due to immune cytokines is steadily increasing the morbidity of cardiovascular diseases (CVD), making them the leading cause of death globally. Nevertheless, improper diagnosis is an important hurdle in case management. Free radicals are one of major factors in producing vascular abnormalities in CVD. Additionally, some other factors such as high blood pressure, myocardial injuries, vascular damage, ventricular hypertrophy, cardiac fibrosis and myocardial necrosis are also the results of free radical-mediated abnormal cardiac activity/function. Of note, Nitric Oxide Synthase (iNOS) is produced in the body at an elevated rate in the presence of free radicals which has been shown to lead to cardiac issues. Furthermore, iNOS is also increased due to cytoplasmic stress, faulty DNA replication and membrane potential impairment. Moreover, abnormal cardiac rhythm has also been reported to be linked to the presence of iNOS. iNOS can also lead to abnormal cardiac function through inhibition of mitochondrial activity and production of pro-inflammatory cytokines. The molecular mechanism of iNOS that leads to CVD is comprehensively summarized in this review so as to aid in drug discovery strategies for the treatment of CVD.

Key words: iNOS, Immunity, Inflammation, Hypertension, vascular damage

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