Abstract:Plasminogen activator inhibitor 1 (PAI-1) also known as serpin E1 or endothelial plasminogen activator inhibitor, is produced from endothelial cells and adipose tissue. PAI-1 inhibits tissue plasminogen activator (tPA) and urokinase (uPA) preventing activation of plasminogen and fibrinolysis. Gestational diabetes mellitus (GDM) is defined as glucose intolerance and hyperglycemia during pregnancy. The underlying mechanism of GDM is due to the reduction of insulin secretion or the development of insulin resistan… Show more
“…Brain IR can be defined as the failure of brain cells to respond to insulin, resulting in impairments in synaptic, metabolic, and immune response functions [ 45 , 46 ]. T2DM is associated with brain IR, and studies suggest that brain IR is a feature of AD; however, whether the two conditions are mechanistically linked or represent unrelated occurrences in ageing is unclear [ 45 , 46 , 47 ]. Herein, statins-induced IR and T2DM could be the possible mechanistic pathway by which statins affect AD pathology.…”
Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.
“…Brain IR can be defined as the failure of brain cells to respond to insulin, resulting in impairments in synaptic, metabolic, and immune response functions [ 45 , 46 ]. T2DM is associated with brain IR, and studies suggest that brain IR is a feature of AD; however, whether the two conditions are mechanistically linked or represent unrelated occurrences in ageing is unclear [ 45 , 46 , 47 ]. Herein, statins-induced IR and T2DM could be the possible mechanistic pathway by which statins affect AD pathology.…”
Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.
“…In addition, DPP4 promotes the progression of coronary atherosclerotic plaques by enhancing monocyte migration and inhibiting the protective endothelial signaling pathway of the glucagon-like peptide. 129 Recently, DPP4 is a potential receptor for entry of SARS-CoV-2, and DPP4 inhibitors might be a potential therapeutic strategy in treating COVID-19 even in nondiabetic patients 130,131 (Figure 2).…”
Coronavirus disease 2019 (COVID‐19) is a novel pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It has been shown that SARS‐CoV‐2 infection‐induced inflammatory and oxidative stress and associated endothelial dysfunction may lead to the development of acute coronary syndrome (ACS). Therefore, this review aimed to ascertain the link between severe SARS‐CoV‐2 infection and ACS. ACS is a spectrum of acute myocardial ischemia due to a sudden decrease in coronary blood flow, ranging from unstable angina to myocardial infarction (MI). Primary or type 1 MI (T1MI) is mainly caused by coronary plaque rupture and/or erosion with subsequent occlusive thrombosis. Secondary or type 2 MI (T2MI) is due to cardiac and systemic disorders without acute coronary atherothrombotic disruption. Acute SARS‐CoV‐2 infection is linked with the development of nonobstructive coronary disorders such as coronary vasospasm, dilated cardiomyopathy, myocardial fibrosis, and myocarditis. Furthermore, SARS‐CoV‐2 infection is associated with systemic inflammation that might affect coronary atherosclerotic plaque stability through augmentation of cardiac preload and afterload. Nevertheless, major coronary vessels with atherosclerotic plaques develop minor inflammation during COVID‐19 since coronary arteries are not initially and primarily targeted by SARS‐CoV‐2 due to low expression of angiotensin‐converting enzyme 2 in coronary vessels. In conclusion, SARS‐CoV‐2 infection through hypercytokinemia, direct cardiomyocyte injury, and dysregulation of the renin‐angiotensin system may aggravate underlying ACS or cause new‐onset T2MI. As well, arrhythmias induced by anti‐COVID‐19 medications could worsen underlying ACS.
“…This effect induces membrane depolarization with increasing intracellular Ca +2 within pancreatic β cells and subsequent insulin release (Najdi et al 2019 ). Glibenclamide is mainly used in the management of type 2 diabetes mellitus (T2DM); however, it is not the first-line therapy in T2DM (Najdi et al 2019 ; Batiha et al 2022 ). Fig.…”
In coronavirus disease 2019 (Covid-19) era, neuroinflammation may develop due to neuronal tropism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or associated immune activation, cytokine storm, and psychological stress. SARS-CoV-2 infection and linked cytokine storm may cause blood–brain barrier (BBB) injury through which activated immune cells and SARS-CoV-2 can pass into the brain causing activation of glial cells with subsequent neuroinflammation. Different therapeutic regimens were suggested to alleviate Covid-19-induced neuroinflammation. Since glibenclamide has anti-inflammatory and neuroprotective effects, it could be effective in mitigation of SARS-CoV-2 infection-induced neuroinflammation. Glibenclamide is a second-generation drug from the sulfonylurea family, which acts by inhibiting the adenosine triphosphate (ATP)-sensitive K channel in the regulatory subunit of type 1 sulfonylurea receptor (SUR-1) in pancreatic β cells. Glibenclamide reduces neuroinflammation and associated BBB injury by inhibiting the nod-like receptor pyrin 3 (NLRP3) inflammasome, oxidative stress, and microglial activation. Therefore, glibenclamide through inhibition of NLRP3 inflammasome, microglial activation, and oxidative stress may attenuate SARS-CoV-2-mediated neuroinflammation.
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