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Association between risk factors for vascular dementia and adiponectin.

Song J, Lee WT, Park KA, Lee JE - Biomed Res Int (2014)

Bottom Line: Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke.Adiponectin plasma levels decrease with age.Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul 120-752, Republic of Korea.

ABSTRACT
Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

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Adiponectin improves vascular cognitive impairment by stimulating NO production. Adiponectin, acting via AdipoR1 and AdipoR2, promotes AMPK phosphorylation and NO production. Increased NO reduces platelet aggregation and increases vasodilation. Consequentially, adiponectin decreases the risk of hypertension and improves vascular cognitive impairment. AMPK: AMP-activated kinase and NO: nitric oxide.
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fig3: Adiponectin improves vascular cognitive impairment by stimulating NO production. Adiponectin, acting via AdipoR1 and AdipoR2, promotes AMPK phosphorylation and NO production. Increased NO reduces platelet aggregation and increases vasodilation. Consequentially, adiponectin decreases the risk of hypertension and improves vascular cognitive impairment. AMPK: AMP-activated kinase and NO: nitric oxide.

Mentions: Hypertension has been reported as the most common risk factor for stroke worldwide and has also been gradually recognized as a risk factor for dementia [149]. Arterial hypertension contributes to the development and progression of cerebrovascular disease [150]. Hypertension exposes the cerebral microvasculature to pulsatile pressure and flow that cause vascular endothelium and smooth muscle cell tearing [151]. Many cross-sectional and longitudinal studies have demonstrated that dementia and VCI are associated with hypertension [152–156]. Therefore, previous studies suggest that hypertension is the most important risk factor for cerebral vessel dysfunction, and it contributes to cognitive decline [157, 158]. Pulse pressure (PP), a marker of arterial stiffness, has been connected with the risk of cognitive decline [159] and AD [160, 161]. Elevated pulse pressure increases the risk of cognitive decline and impaired language abilities [162]. Decreased blood pressure (BP) is a clinical manifestation of dementia in elderly subjects [163, 164]. Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) are crucial regulators of vascular homeostasis and, in particular, endothelial function [165, 166]. Endothelium-derived NO is a beneficial factor that promotes vasodilation and inhibits platelet aggregation, monocyte adhesion, and smooth muscle cell proliferation [167]. Adiponectin, acting via AdipoR1 and AdipoR2, promotes NO production through AMPK signaling pathway activation. AMPK activates eNOS through phosphorylation at Ser1177 and facilitates complex formation between eNOS and heat shock protein 90 (HSP-90), which is required for eNOS activation [167]. Adiponectin knockout mice have reduced endothelial NO levels in vessel walls [168]. Adiponectin inhibits the inflammatory response and causes vasodilatation largely through AMPK/eNOS [169–172]. Adiponectin-induced AMPK signaling promotes phosphatidylinositol 3-kinase-Akt signaling, leading to angiogenic growth factor synthesis [170, 173]. A recent study also suggests that adiponectin inhibits vascular endothelial growth factor- (VEGF-) induced ROS generation and has an antioxidant role in the vasculature [174]. These actions of adiponectin are also mediated via inhibition of growth factor-stimulated extracellular signal regulated kinase (ERK) signaling. In addition, several studies indicate that adiponectin plays a role in the regulation of microvascular network flow and function [175, 176]. Some clinical research demonstrates that plasma adiponectin levels are positively associated with arterial vasodilation [177]. Considering the role of adiponectin in vascular function, decreased adiponectin raises the risk of hypertension. Figure 3 shows that adiponectin increases AMPK phosphorylation and NO production. Platelet aggregation is decreased and vasodilation is increased due to NO production. Finally, adiponectin decreases the risk of hypertension and improves vascular cognitive impairment (Figure 3).


Association between risk factors for vascular dementia and adiponectin.

Song J, Lee WT, Park KA, Lee JE - Biomed Res Int (2014)

Adiponectin improves vascular cognitive impairment by stimulating NO production. Adiponectin, acting via AdipoR1 and AdipoR2, promotes AMPK phosphorylation and NO production. Increased NO reduces platelet aggregation and increases vasodilation. Consequentially, adiponectin decreases the risk of hypertension and improves vascular cognitive impairment. AMPK: AMP-activated kinase and NO: nitric oxide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016875&req=5

fig3: Adiponectin improves vascular cognitive impairment by stimulating NO production. Adiponectin, acting via AdipoR1 and AdipoR2, promotes AMPK phosphorylation and NO production. Increased NO reduces platelet aggregation and increases vasodilation. Consequentially, adiponectin decreases the risk of hypertension and improves vascular cognitive impairment. AMPK: AMP-activated kinase and NO: nitric oxide.
Mentions: Hypertension has been reported as the most common risk factor for stroke worldwide and has also been gradually recognized as a risk factor for dementia [149]. Arterial hypertension contributes to the development and progression of cerebrovascular disease [150]. Hypertension exposes the cerebral microvasculature to pulsatile pressure and flow that cause vascular endothelium and smooth muscle cell tearing [151]. Many cross-sectional and longitudinal studies have demonstrated that dementia and VCI are associated with hypertension [152–156]. Therefore, previous studies suggest that hypertension is the most important risk factor for cerebral vessel dysfunction, and it contributes to cognitive decline [157, 158]. Pulse pressure (PP), a marker of arterial stiffness, has been connected with the risk of cognitive decline [159] and AD [160, 161]. Elevated pulse pressure increases the risk of cognitive decline and impaired language abilities [162]. Decreased blood pressure (BP) is a clinical manifestation of dementia in elderly subjects [163, 164]. Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) are crucial regulators of vascular homeostasis and, in particular, endothelial function [165, 166]. Endothelium-derived NO is a beneficial factor that promotes vasodilation and inhibits platelet aggregation, monocyte adhesion, and smooth muscle cell proliferation [167]. Adiponectin, acting via AdipoR1 and AdipoR2, promotes NO production through AMPK signaling pathway activation. AMPK activates eNOS through phosphorylation at Ser1177 and facilitates complex formation between eNOS and heat shock protein 90 (HSP-90), which is required for eNOS activation [167]. Adiponectin knockout mice have reduced endothelial NO levels in vessel walls [168]. Adiponectin inhibits the inflammatory response and causes vasodilatation largely through AMPK/eNOS [169–172]. Adiponectin-induced AMPK signaling promotes phosphatidylinositol 3-kinase-Akt signaling, leading to angiogenic growth factor synthesis [170, 173]. A recent study also suggests that adiponectin inhibits vascular endothelial growth factor- (VEGF-) induced ROS generation and has an antioxidant role in the vasculature [174]. These actions of adiponectin are also mediated via inhibition of growth factor-stimulated extracellular signal regulated kinase (ERK) signaling. In addition, several studies indicate that adiponectin plays a role in the regulation of microvascular network flow and function [175, 176]. Some clinical research demonstrates that plasma adiponectin levels are positively associated with arterial vasodilation [177]. Considering the role of adiponectin in vascular function, decreased adiponectin raises the risk of hypertension. Figure 3 shows that adiponectin increases AMPK phosphorylation and NO production. Platelet aggregation is decreased and vasodilation is increased due to NO production. Finally, adiponectin decreases the risk of hypertension and improves vascular cognitive impairment (Figure 3).

Bottom Line: Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke.Adiponectin plasma levels decrease with age.Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul 120-752, Republic of Korea.

ABSTRACT
Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

Show MeSH
Related in: MedlinePlus