Changes of the coronary arteries and cardiac microvasculature with aging: Implications for translational research and clinical practice

Piccirillo, Francesco; Carpenito, Myriam; Verolino, Giuseppe; Chello, Camilla; Nusca, Annunziata; Lusini, Mario; Spadaccio, Cristiano; Nappi, Francesco; Sciascio, Germano Di; Nenna, Antonio

doi:10.1016/j.mad.2019.111161

Cited by 32 publications

(27 citation statements)

References 244 publications

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“…Additionally, our research indicated that after inhibition of CD38 activity on the aortic valve surface, there was a significant decrease in NAD + catabolism. It is well known that CD38 contributes to the regulation of metabolism at the physiological level and is involved in the pathogenesis of multiple conditions, including ageing, heart disease and inflammation 8,30‐32 . Increased CD38 activity in the cardiovascular system can be the result of many factors.…”

Section: Discussionmentioning

confidence: 99%

The new insight into extracellular NAD⁺ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

Jabłońska

Kutryb–Zajac

Mierzejewska

et al. 2021

J Cellular Molecular Medi

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Nicotinamide adenine dinucleotide (NAD+) is crucial for cell energy metabolism and many signalling processes. Recently, we proved the role of ecto‐enzymes in controlling adenine nucleotide–dependent pathways during calcific aortic valve disease (CAVD). This study aimed to investigate extracellular hydrolysis of NAD+ and mononucleotide nicotinamide (NMN) in aortic valves and aorta fragments of CAVD patients and on the inner aortic surface of ecto‐5′‐nucleotidase knockout mice (CD73−/−). Human non‐stenotic valves (n = 10) actively converted NAD+ and NMN via both CD73 and NAD+‐glycohydrolase (CD38) according to our analysis with RP‐HPLC and immunofluorescence. In stenotic valves (n = 50), due to reduced CD73 activity, NAD+ was degraded predominantly by CD38 and additionally by ALP and eNPP1. CAVD patients had significantly higher hydrolytic rates of NAD+ (0.81 ± 0.07 vs 0.56 ± 0.10) and NMN (1.12 ± 0.10 vs 0.71 ± 0.08 nmol/min/cm2) compared with controls. CD38 was also primarily engaged in human vascular NAD+ metabolism. Studies using specific ecto‐enzyme inhibitors and CD73−/− mice confirmed that CD73 is not the only enzyme involved in NAD+ and NMN hydrolysis and that CD38 had a significant contribution to these pathways. Modifications of extracellular NAD+ and NMN metabolism in aortic valve cells may be particularly important in valve pathology and could be a potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

The new insight into extracellular NAD⁺ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

Jabłońska

Kutryb–Zajac

Mierzejewska

et al. 2021

J Cellular Molecular Medi

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“…Aging is one of the most essential risk factors for vascular diseases and subsequent cardiovascular and cerebrovascular events (87). Aging affects the homeostasis of human vessels and alters their susceptibility to pathological states such as diabetes, hypertension, and atherosclerosis (195). Severer oxidative damage was also found in the aortic media of older people (162).…”

Section: Other Factors Associated With Vascular Diseasementioning

confidence: 99%

Metabolism of vascular smooth muscle cells in vascular diseases

Shi

Yang

Cheng

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

194

120

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Vascular smooth muscle cells (VSMCs) are the fundamental component of the medial layer of arteries and are essential for arterial physiology and pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill the bio-energetic and biosynthetic requirements. During vascular injury, VSMCs switch from a quiescent "contractile" phenotype to a highly migratory and proliferative "synthetic" phenotype. Recent studies find that the phenotype switching of VSMCs is driven by a metabolic switch. Metabolic pathways, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, have distinct, indispensable roles in normal and dysfunctional vasculature. VSMCs metabolism is also related to the metabolism of endothelial cells. In the present review, we present a brief overview of VSMCs metabolism, and how it regulates the progression of several vascular diseases, including atherosclerosis, systemic hypertension, diabetes, pulmonary hypertension, vascular calcification, and aneurysms, and the effect of the risk factors for vascular disease (aging, cigarette smoking and excessive alcohol drinking) on VSMCs metabolism, to clarify the role of VSMCs metabolism in the key pathological process.

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“…Parenchymal arterioles and large arteries produce vascular resistance in the brain that occurs in larger arteries having regular cerebral blood flow resulting in vascular endothelial dysfunction due to interfered neurovascular coupling commonly seen in women. Synthesis of nitric oxide occurs from arginine to citrulline into nitric oxide with the help of enzyme endothelin nitric oxide synthase involving tetrahydrobiopterin due to impaired endothelin function oxidation of this cofactor; tetrahydrobiopterin takes place making the change in a final by-product that form free radicals instead of nitric oxide [ 93 , 94 ]. Nitric oxide synthase is an enzyme that constitutes of three members, where two are its isoform neuronal NOS (nNOS) and endothelial NOS (eNOS); both are calcium-dependent enzymes; another enzyme is inducible NOS (iNOS) and this is a calcium-independent enzyme.…”

Section: Endothelin Mechanism Contributing To Alzheimer's Diseasementioning

confidence: 99%

Targeting Endothelin in Alzheimer’s Disease: A Promising Therapeutic Approach

Sharma

Behl

Kumar

et al. 2021

BioMed Research International

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Endothelin is a chemical mediator that helps in maintaining balance within the blood-brain barrier by regulating the levels of toxicants and molecules which pass through the brain, suggesting that a rise in its production determines Alzheimer’s disease. The inequity in the amyloid β occurs due to a problem in its clearance from the brain initiating the production of reactive oxygen species and superoxide that activates a cascade wherein the release of inflammatory mediators and various enzymes like endothelin-converting enzymes take place. Furthermore, the cascade increases the levels of endothelin in the brain from endothelial cells. Endothelin levels are upregulated, which can be regulated by modulating the action of endothelin-converting enzymes and endothelin receptors. Hence, endothelin paves a pathway in the treatment of Alzheimer’s disease. In this article, we have covered various mechanisms and preclinical studies that support and direct endothelin involvement in the progression of Alzheimer’s disease by using various search tools such as PubMed, Science Direct, and Medline. Conclusive outcome data were extracted that all together defy contrivance pathways, potential drugs, endothelin receptors, and endothelin enzymes in our article giving profound importance to target endothelin for prevention and treatment of Alzheimer’s disease.

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Changes of the coronary arteries and cardiac microvasculature with aging: Implications for translational research and clinical practice

Cited by 32 publications

References 244 publications

The new insight into extracellular NAD⁺ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

The new insight into extracellular NAD⁺ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

Metabolism of vascular smooth muscle cells in vascular diseases

Targeting Endothelin in Alzheimer’s Disease: A Promising Therapeutic Approach

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Changes of the coronary arteries and cardiac microvasculature with aging: Implications for translational research and clinical practice

Cited by 32 publications

References 244 publications

The new insight into extracellular NAD+ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

The new insight into extracellular NAD+ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

Metabolism of vascular smooth muscle cells in vascular diseases

Targeting Endothelin in Alzheimer’s Disease: A Promising Therapeutic Approach

Contact Info

Product

Resources

About

The new insight into extracellular NAD⁺ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease

The new insight into extracellular NAD⁺ degradation‐the contribution of CD38 and CD73 in calcific aortic valve disease