Proinflammation, profibrosis, and arterial aging

Wang, Mingyi; Monticone, Robert E.; McGraw, Kimberly R.

doi:10.1002/agm2.12099

Cited by 20 publications

(19 citation statements)

References 107 publications

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“…Studies found increased levels of several MMPs (e.g., MMP-2, -3, -9) in the blood of TAK patients; other studies did not support these findings [98]. MMPs have been implicated in the process of vascular aging by directly contributing to wall fibrosis and stiffening [99,100]. A propensity of GCA and possible TAK monocytes and macrophages to release excessive MMPs may be relevant for the loss of tissue tolerance and, in a feed-forward loop, lead to accelerated aging of the affected vessels.…”

Section: Pathogenic Dendritic Cells and Macrophages In Large-vessel V...mentioning

confidence: 99%

Age as a risk factor in vasculitis

et al. 2022

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Two vasculitides, giant cell arteritis (GCA) and Takayasu arteritis (TAK), are recognized as autoimmune and autoinflammatory diseases that manifest exclusively within the aorta and its large branches. In both entities, the age of the affected host is a critical risk factor. TAK manifests during the 2nd–4th decade of life, occurring while the immune system is at its height of performance. GCA is a disease of older individuals, with infrequent cases during the 6th decade and peak incidence during the 8th decade of life. In both vasculitides, macrophages and T cells infiltrate into the adventitia and media of affected vessels, induce granulomatous inflammation, cause vessel wall destruction, and reprogram vascular cells to drive adventitial and neointimal expansion. In GCA, abnormal immunity originates in an aged immune system and evolves within the aged vascular microenvironment. One hallmark of the aging immune system is the preferential loss of CD8+ T cell function. Accordingly, in GCA but not in TAK, CD8+ effector T cells play a negligible role and anti-inflammatory CD8+ T regulatory cells are selectively impaired. Here, we review current evidence of how the process of immunosenescence impacts the risk for GCA and how fundamental differences in the age of the immune system translate into differences in the granulomatous immunopathology of TAK versus GCA.

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Section: Pathogenic Dendritic Cells and Macrophages In Large-vessel V...mentioning

confidence: 99%

Age as a risk factor in vasculitis

et al. 2022

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“…Further, there is interplay between these biochemical and mechanical factors that govern overall aortic stiffness (Lakatta & Levy, 2003; Wang et al . 2020). A limitation of the present study is that we did not complement our in vivo aortic stiffness measures with ex vivo assessments of the elastic modulus of the aorta or with assessment of collagen and elastin protein content so we cannot precisely delineate the mechanisms by which T cells contribute to aortic stiffness with advancing age.…”

Section: Discussionmentioning

confidence: 99%

T cells mediate cell non‐autonomous arterial ageing in mice

Trott

Machin

Phuong

et al. 2021

The Journal of Physiology

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Key points Increased large artery stiffness and impaired endothelium‐dependent dilatation occur with advanced age. We sought to determine whether T cells mechanistically contribute to age‐related arterial dysfunction. We found that old mice exhibited greater proinflammatory T cell accumulation around both the aorta and mesenteric arteries. Pharmacologic depletion or genetic deletion of T cells in old mice resulted in ameliorated large artery stiffness and greater endothelium‐dependent dilatation compared with mice with T cells intact. Abstract Ageing of the arteries is characterized by increased large artery stiffness and impaired endothelium‐dependent dilatation. T cells contribute to hypertension in acute rodent models but whether they contribute to chronic age‐related arterial dysfunction is unknown. To determine whether T cells directly mediate age‐related arterial dysfunction, we examined large elastic artery and resistance artery function in young (4–6 months) and old (22–24 months) wild‐type mice treated with anti‐CD3 F(ab’2) fragments to deplete T cells (150 μg, i.p. every 7 days for 28 days) or isotype control fragments. Old mice exhibited greater numbers of T cells in both aorta and mesenteric vasculature when compared with young mice. Old mice treated with anti‐CD3 fragments exhibited depletion of T cells in blood, spleen, aorta and mesenteric vasculature. Old mice also exhibited greater numbers of aortic and mesenteric IFN‐γ and TNF‐α‐producing T cells when compared with young mice. Old control mice exhibited greater large artery stiffness and impaired resistance artery endothelium‐dependent dilatation in comparison with young mice. In old mice, large artery stiffness was ameliorated with anti‐CD3 treatment. Anti‐CD3‐treated old mice also exhibited greater endothelium‐dependent dilatation than age‐matched controls. We also examined arterial function in young and old Rag‐1–/– mice, which lack lymphocytes. Rag‐1–/– mice exhibited blunted increases in large artery stiffness with age compared with wild‐type mice. Old Rag‐1–/– mice also exhibited greater endothelium‐dependent dilatation compared with old wild‐type mice. Collectively, these results demonstrate that T cells play an important role in age‐related arterial dysfunction.

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“…The development of increased arterial stiffness is related to arteriosclerosis, a process which is driven by endothelial dysfunction (ED) and vascular ageing [12]. In systolic HF, due to a complex pathophysiological mechanism (e.g., decreased arterial wall tension, neurohormonal activation) there is a fall in endothelial nitric oxide (NO) synthase expression, with low endothelium-derived NO production.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of arterial stiffness in systolic heart failure

Fehérvári¹,

Szabó

Kocsis³

et al. 2021

Acta Marisiensis - Seria Medica

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Objective: Micro- and macrovascular changes can occur in heart failure, and could influence its prognosis and management. In a prospective study, we proposed the evaluation of arterial stiffness (macrovascular function) and its correlations in patients with systolic heart failure. Methods: 40 patients (32 men, 8 women, mean age 63±2.9 years), with hemodynamically stable systolic heart failure (left ventricular ejection fraction, EF<40%) were enrolled in the study. In every patient, beyond routine explorations (ECG, cardiac and carotid ultrasound, laboratory measurements), arterial stiffness was assessed by measuring pulse wave velocity (PWV). The correlations of PWV with clinical and echo-cardiographic characteristics were studied using t-test and chi-square test (p<0.05 being considered for statistical significance). Results: The average PWV was 8.55±2.2 m/s, and 16 patients had increased PWV (>10 m/s). We found significantly higher PWV values in patients older than 65 years (p<0.001), in patients with eGFR <60 ml/min/1.73 m2 (p<0.001), hypertension (p=0.006), and increased (>1 mm) carotid intima-media thickness (p=0.016). PWV was found to be significantly lower when EF was <30% (p=0.049). Furthermore, the presence of an increased PWV was correlated significantly with age (p<0.001), and (with borderline significance) with eGFR <60 ml/min/1.73 m2 and, inversely, with EF<30%. Conclusions: Increased arterial stiffness reflected by high PWV is frequently present in patients with systolic heart failure, and is mainly correlated with general risk factors of arterial involvement. Low EF, due to low stroke volume and decreased systolic arterial wall tension can influence the values and the interpretation of PWV.

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Proinflammation, profibrosis, and arterial aging

Cited by 20 publications

References 107 publications

Age as a risk factor in vasculitis

Age as a risk factor in vasculitis

T cells mediate cell non‐autonomous arterial ageing in mice

Evaluation of arterial stiffness in systolic heart failure

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