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.

SummaryBackgroundPre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery.AimsThe objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk.MethodsThis was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum.ResultsAt one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks’ gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11–10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not.ConclusionWomen who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

African American (AA) race is an independent risk factor for vascular disease (e.g., hypertension) [1,2]. Hypertension disproportionately affects AAs, regardless of admixture [3], coupled with increased severity of hypertension and nearly a twofold increase in mortality associated with cardiovascular disease [4], thus revealing the epidemiological racial disparity and public health impact regarding hypertension [5,6]. Therefore, investigations are necessary to understand potential mechanism(s) that ultimately lead to premature and exacerbated hypertension-related cardiovascular diseases (e.g., stroke, kidney disease, hypertensive neuropathy, heart dysfunction) and end-organ failure in AA.Endothelial Dysfunction (EnDy), which can precede hypertension, has been shown to be greater in AA [7,8]. EnDy is characterized by a chronic low-grade inflammatory state of the endothelium and is marked by an exacerbated immune and oxidative stress response to inflammation. In vitro, Kalinowski et al. [1] showed that AA Human Umbilical Vein Endothelial Cells (HUVEC) exhibit EnDy marked by increased oxidative stress (e.g., superoxide and peroxynitrite production; Reactive Oxygen Species (ROS) and consequent reduced nitric oxide (NOx) bioavailability). Studies have previously shown that AA had significantly greater ROS in vitro and in vivo [9,10], and had greater circulating inflammatory endothelial microparticles (a novel biomarker of EnDy) [11,12]. One mechanistic explanation of these in vitro observations was that AA Endothelial Cells (EC) exhibited greater expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, increased basal inflammation, and lower antioxidant capacity [9] compared to Caucasian (CA) HUVEC that significantly improved in response to in vitro exercise mimetic (i.e., laminar shear stress)

Using multiple mouse models, we explored the impact of aging on the size and severity of atherosclerotic lesions. In young, middle-aged and old apolipoprotein E knockout mice (ApoE−/−) fed an atherogenic diet (AD) for 3–8 weeks, plaque/atheroma formation in the descending aorta and aortic root, and atheroma development in the carotid in response to partial carotid ligation (PCL) were assessed. Total and LDL cholesterol, and triglycerides were higher in old compared to both other age groups, regardless of AD duration. Aortic plaque burden increased with AD duration in all ages. The size and plaque morphology grade of aortic root atheromas was higher with age; however, there was no effect of age on the size or severity of carotid atheromas after PCL. We additionally induced hyperlipidemia in young and old C57BL/6 mice by adeno-associated virus mediated upregulation of LDL receptor regulator, Pcsk9, and 5 weeks of AD. Despite lower cholesterol in old compared to young Pcsk9 mice, there was a greater size and severity of aortic root atheromas in old mice. However, like the ApoE−/− mice, there was no effect of age on size or severity of PCL-induced carotid artery atheromas in Pcsk9 mice. Together, these results suggest that aging increases the size and severity of spontaneous aortic atheromas.