Senescent Vascular Smooth Muscle Cells Drive Inflammation Through an Interleukin-1α–Dependent Senescence-Associated Secretory Phenotype

Gardner, Sarah; Humphry, Melanie; Bennett, Martin R.; Clarke, Murray C.H.

doi:10.1161/atvbaha.115.305896

Cited by 217 publications

(185 citation statements)

References 41 publications

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“…The increase in IL-1β is in accord with a previous observation by our group showing increased aortic IL-1β concentrations in with age in mice [10]. IL-10 is an anti-inflammatory cytokine and mice deficient in IL-10 develop arterial dysfunction at a younger age than wild type controls [39]. This suggests that the age-related increase in IL-10 may be a compensatory response in attempt to preserve arterial function with age.…”

Section: Discussionsupporting

confidence: 89%

Selected life-extending interventions reduce arterial CXCL10 and macrophage colony-stimulating factor in aged mouse arteries

2017

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Cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Aging is the most predictive risk factor for CVD and is associated with arterial inflammation which contributes to increased CVD risk. Although age-related arterial inflammation has been described in both humans and animals, only a limited number of inflammatory mediators, cytokines and chemokines have been identified. In this investigation we sought to determine whether lifespan extending interventions, including crowded litter early life nutrient deprivation (CL), traditional lifelong caloric restriction (CR) and lifelong Rapamycin treatment (Rap) would attenuate age-related arterial inflammation using multi analyte profiling. Aortas from Young (4–6 months), Old (22 months), Old CL, Old CR and Old Rap mice were homogenized and cytokine concentrations were assessed using Luminex Multi Analyte Profiling. Chemokines involved in immune cell recruitment, such as CCL2, CXCL9, CXCL10, GMCSF and MCSF, were increased in Old vs. Young (p < 0.05). The age-related increase of CXCL10 was prevented by CR (p < 0.05 vs. Old). MSCF concentrations were lower in aortas of Rap treated mice (p < 0.05 vs. Old). Interleukins (IL), IL-1α, IL-1β and IL-10, were also greater in Old vs. Young mice (p < 0.05). These data demonstrate selected lifespan extending interventions can prevent or limit age-related increases in selected aortic chemokines.

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Section: Discussionsupporting

confidence: 89%

Selected life-extending interventions reduce arterial CXCL10 and macrophage colony-stimulating factor in aged mouse arteries

2017

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“…71 Interestingly, another ATVB publication by Gardner, et al suggested that senescent VSMCs may be active participants in CVD processes and assume a pro-inflammatory state and secrete factors that promote chemotaxis of mononuclear cells in vitro and in vivo and that release active MMP-9, secrete less collagen, and prime endothelial cells and VSMCs to a pro-inflammatory state. 72 And while this was established in a model of atherosclerosis, whether this VSMC phenotype plays a direct role in arterial stiffness remains to be investigated.…”

Section: Underlying Mechanisms Of Arterial Stiffeningmentioning

confidence: 99%

Killing Me Unsoftly

Lyle

Raaz

2017

ATVB

112

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The aorta is a blood vessel that provides a low resistance path for blood flow directed from the heart to peripheral organs and tissues. However, the aorta has another central hemodynamic function whereby the elastic nature of the aortic wall provides a significant biomechanical buffering capacity complementing the pulsatile cardiac blood flow and this is often referred to as Windkessel function. Stiffening of the arterial wall leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function. In this review article, we aim to provide a short general overview of some of the most common mechanisms that contribute to increased arterial stiffness, the consequences of arterial stiffening, and the clinical conditions in which arterial stiffness occurs with a focus on recent advancements in the field.

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“…97 Moreover, a recent study displayed that senescent human VSMCs develop a proinflammatory state known as SASP. 98 These results suggest that inflammation associated with the normal aging process contributes to the onset of age-related diseases. Ang II stimulation is one of the factors responsible for the cellular senescence of the vasculature.…”

Section: Aging In the Vasculaturementioning

confidence: 89%

Macromolecular Degradation Systems and Cardiovascular Aging

Nakayama

Nishida

Otsu³

2016

Circulation Research

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7Cardiovascular aging or age-associated cardiovascular diseases include atherosclerosis, coronary artery disease, hypertension, heart failure, and atrial fibrillation. In addition, aged hearts are characterized by decreased contractility, impaired diastolic function, and atrium dilatation, indicating that both the functional and the morphological alterations that result in these diseases of the heart occur during the aging process. Abstract: Aging-related cardiovascular diseases are a rapidly increasing problem worldwide. Cardiac aging demonstrates progressive decline of diastolic dysfunction of ventricle and increase in ventricular and arterial stiffness accompanied by increased fibrosis stimulated by angiotensin II and proinflammatory cytokines. Reactive oxygen species and multiple signaling pathways on cellular senescence play major roles in the process. Aging is also associated with an alteration in steady state of macromolecular dynamics including a dysfunction of protein synthesis and degradation. Currently, impaired macromolecular degradation is considered to be closely related to enhanced inflammation and be involved in the process and mechanism of cardiac aging. Herein, we review the role and mechanisms of the degradation system of intracellular macromolecules in the process and pathophysiology of cardiovascular aging.

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Senescent Vascular Smooth Muscle Cells Drive Inflammation Through an Interleukin-1α–Dependent Senescence-Associated Secretory Phenotype

Abstract: Supplemental Digital Content is available in the text.

Cited by 217 publications

References 41 publications

Selected life-extending interventions reduce arterial CXCL10 and macrophage colony-stimulating factor in aged mouse arteries

Selected life-extending interventions reduce arterial CXCL10 and macrophage colony-stimulating factor in aged mouse arteries

Killing Me Unsoftly

Macromolecular Degradation Systems and Cardiovascular Aging

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