The aging endothelium

Ting, Ka Ka; Coleman, Paul R.; Zhao, Yang; Vadas, Mathew A.; Gamble, Jennifer R.

doi:10.1530/vb-20-0013

Cited by 25 publications

(15 citation statements)

References 146 publications

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“…In old mice (>12 months), vessel dysfunction is accompanied by irreversible histological changes characterized by atherosclerotic plaques and vascular wall remodelling [ 19 ]. In the present study, a relatively early advanced life span was investigated.…”

Section: Resultsmentioning

confidence: 99%

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Zhong

Boral

et al. 2021

IJMS

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Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10−6 mol L−1) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10−6 mol L−1) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.

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Section: Resultsmentioning

confidence: 99%

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Zhong

Boral

et al. 2021

IJMS

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“…29 The endothelium that dies prematurely cannot be efficiently repopulated, resulting in microvessels devoid of endothelium, the critical stimulus for basement membrane zone reduplication. 30 A procoagulant state in the context of CCV has been previously reported in the literature, specifically in a middle-aged woman with a history of prothrombin G20210A thrombophilia and biopsy-proven CCV. 31 Vascular thrombosis is a stimulus to endogenous nitrous oxide release from endothelium and leads to vascular relaxation hallmarked by vascular dilatation.…”

Section: Discussionmentioning

confidence: 79%

“…Inhibition of endothelial growth leading to CCV helps support the concept that a diminished endothelial cell progenitor pool might be a key event 29 . The endothelium that dies prematurely cannot be efficiently repopulated, resulting in microvessels devoid of endothelium, the critical stimulus for basement membrane zone reduplication 30 …”

Section: Discussionmentioning

confidence: 82%

Cutaneous collagenous vasculopathy: A report of three cases

et al. 2022

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Cutaneous collagenous vasculopathy is a rare pauci‐inflammatory, superficial, cutaneous vasculopathy characterized by progressive fine‐branching telangiectasias clinically, while light microscopically one observes dilated venules and capillaries within the superficial dermis exhibiting excessive Type IV collagen within the vessel wall. We present three cases of collagenous vasculopathy. Two cases were associated with certain autoimmune stigmata, including a positive serologic anti‐endothelial cell antibody assay and positive lupus anticoagulant in one, while the third case had positive anti‐ribonucleoprotein (RNP) antibodies. The latter case was associated with chronic hydroxyurea therapy for an underlying myeloproliferative disorder. We explore the role of immune‐ and non‐immune‐based endothelial cell injury in the pathogenesis of collagenous vasculopathy.

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“…Clinical trials have shown that targeting inflammation can reduce cardiovascular events [ 317 ]. The healthy vascular endothelium inhibits platelet adhesion to the surface [ 325 ] but cardiovascular risk factors (e.g., hypertension) increase oxygen free radical production, causing the endothelium to switch to a pro-coagulant, pro-inflammatory and vasoconstrictor phenotype [ 326 , 327 ].…”

Section: Resultsmentioning

confidence: 99%

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

Tyler

2022

Nat. Prod. Bioprospect.

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Alzheimer’s disease (AD) is progressive and ultimately fatal, with current drugs failing to reverse and cure it. This study aimed to find plant species which may provide therapeutic bioactivities targeted to causal agents proposed to be driving AD. A novel toolkit methodology was employed, whereby clinical symptoms were translated into categories recognized in ethnomedicine. These categories were applied to find plant species with therapeutic effects, mined from ethnomedical surveys. Survey locations were mapped to assess how this data is at risk. Bioactivities were found of therapeutic relevance to 15 hypothesised causal bases for AD. 107 species with an ethnological report of memory improvement demonstrated therapeutic activity for all these 15 causal bases. The majority of the surveys were found to reside within biodiversity hotspots (centres of high biodiversity under threat), with loss of traditional knowledge the most common threat. Our findings suggest that the documented plants provide a large resource of AD therapeutic potential. In demonstrating bioactivities targeted to these causal bases, such plants may have the capacity to reduce or reverse AD, with promise as drug leads to target multiple AD hallmarks. However, there is a need to preserve ethnomedical knowledge, and the habitats on which this knowledge depends. Graphical Abstract

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The aging endothelium

Cited by 25 publications

References 146 publications

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Cutaneous collagenous vasculopathy: A report of three cases

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

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