Circadian levels of proprotein convertase subtilisin/kexin type 9 as new target for chronotherapy with monoclonal antibodies

The high prevalence of mortality and morbidity due to cardiovascular diseases (CVDs) indicates that there is a large unmet medical need for new and effective agents that are also well tolerated and safe, especially for patients unable to either tolerate statins or achieve optimal low-density lipoprotein cholesterol (LDL-C) which is a major risk factor of myocardial infarction and stroke. There is evidence that proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration might accelerate atherosclerosis by promoting inflammation, endothelial dysfunction, and hypertension by mechanisms independent of the LDL receptor. Recent clinical trials with PCSK9 inhibitor monoclonal antibodies indicate that with present doses and mode of administration, substantial benefit can be achieved in reducing cardiovascular events with modest reduction in mortality. There is an unmet need to find out PCSK9 metabolism in relation to other risk factors of CVDs, with respect to PCSK9 concentrations according to time structure. This is important because LDL receptor activity and synthesis of cholesterol in the hepatocyte as well as PCSL9 gene activity may be circadian periodic. It is possible that knowledge about circadian concentration of PCSK9, every 4 hours, according to time structure may provide information about its circadian bioavailability and bioactivity. An agent may be highly bioavailable but may not be bioactive due to circadian dysfunction. Chronotherapy with PCSK9 inhibitors according to time structure may decrease their adverse effects and increase efficacy, compared to same dose administered blindly. © 2018 Nova Science Publishers, Inc.

Number of issue
2
Language
English
Pages
153-162
Status
Published
Volume
10
Year
2018
Organizations
  • 1 Department of Veterinary Medicine of the Agrarian and Technology Institute, People’s Friendship University of Russia, Moscow, Russian Federation
  • 2 Halberg Hospital and Research Institute, Moradabad, India
  • 3 Faculty of Medicine, PJ Safaric University University, Kosice, Slovakia
  • 4 Division of Chronomedicine, Department of Pathophysiology, People’s Friendship University of Russia, Moscow, Russian Federation
  • 5 Department of Normal Physiology, People’s Friendship University of Russia, Russian Federation
  • 6 Department of Anatomy, People’s Friendship University of Russia, Moscow, Russian Federation
  • 7 VA Frolov Department of Pathology and Pathophysiology, Moscow, Russian Federation
Keywords
Bioavailability and bioactivity; Chronotherapy; Circadian; Monoclonal antibody
Date of creation
20.04.2021
Date of change
20.04.2021
Short link
https://repository.rudn.ru/en/records/article/record/72925/
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