Erratum to‘Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans’

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.

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Abstract P161: Inspiratory Muscle Training and Aerobic Training in the Treatment of Hypertension: Baroreflex Sensitivity, Sympathetic Activity and Endothelial Function Responses

Hypertension ◽

10.1161/hyp.68.suppl_1.p161 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Janaina B Ferreira ◽

Valéria Hong ◽

Otávio Coelho ◽

Silvia Cavasin ◽

Fernando Santos ◽

...

Keyword(s):

Blood Pressure ◽

Endothelial Function ◽

Arterial Hypertension ◽

Vascular Function ◽

Sympathetic Activity ◽

Baroreflex Sensitivity ◽

Aerobic Training ◽

Inspiratory Muscle ◽

Inspiratory Muscle Training ◽

Muscle Training

Arterial hypertension is associated to sympathetic hyperactivity and endothelial dysfunction. Aerobic training (AT) is highly recommended to improve vascular function minimizing complications and Inspiratory muscle training (IMT) has demonstrated beneficial effects in this population, especially improving cardiovascular autonomic control. We sought to observe the effects of both training modalities on baroreflex sensitivity, sympathetic activity and endothelial function, in patients with controlled arterial hypertension. 10 patients (55±4 years old, both genders) were included and allocated into two groups: IMT (n=5, 7days/week, 30min/day, load=30%PImax) and AT (n=5, 2days/week, 1hour/day, load=70%HRmax). Both training protocols were performed during 12 weeks. Blood pressure (BP) and heart rate (HR) signals were recorded before and after protocols, as well as the other evaluations, by pulse telemetry (Finometer®PRO) and ECG (PowerLab®). Arterial baroreflex sensitivity was analysed by sequence method. Sympathetic activity was evaluated by microneurography (PowerLab®) and the endothelial function was evaluated by flow mediated dilation (EnVisor CHD, Philips, Bothell, WA, USA). After 12 weeks treatment IMT improved baroreflex sensitvity to both tachycardic and bradycardic responses respectively (BRR Down Gain (mean): IMT=26.51(±1.7)vs15.57(±6.7), AT=13.94(±5.5)vs17.92(±1.6); BRR Up Gain (mean): IMT=17.16(±1.2)vs16.28(±1.1), AT=12.39(±5)vs12.69(±3.3)). Additionally, we observed reduction of sympathetic activity in both groups (IMT:33.23±11.79vs25.07±13.28; AT:29.88±7.07vs24.09±6.37) and improvement of endothelial function independent of the treatment (IMT:6.4±2.18vs7.22±2.08; AT:5.49±7.43vs7.06±3.12). Regarding the responses to inspiratory muscle training and aerobic training on autonomic cardiovascular control and endothelial function in Hypertension, we demonstrated for the first time that IMT and AT present quite similar effects in patients with controlled blood pressure.

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Coexistence of obstructive sleep apnea and telomerase activity, concentration of selected adipose tissue hormones and vascular endothelial function in patients with arterial hypertension

Respiratory Medicine ◽

10.1016/j.rmed.2019.05.009 ◽

2019 ◽

Vol 153 ◽

pp. 20-25 ◽

Cited By ~ 1

Author(s):

Helena Martynowicz ◽

Olga Kornafel-Flak ◽

Dominika Urbanik ◽

Łukasz Łaczmański ◽

Małgorzata Sobieszczańska ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Adipose Tissue ◽

Sleep Apnea ◽

Endothelial Function ◽

Arterial Hypertension ◽

Activity Concentration ◽

Telomerase Activity ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Obstructive Sleep

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Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism

European Heart Journal ◽

10.1093/eurheartj/ehz459 ◽

2019 ◽

Vol 41 (26) ◽

pp. 2487-2497 ◽

Cited By ~ 13

Author(s):

Annibale Alessandro Puca ◽

Albino Carrizzo ◽

Chiara Spinelli ◽

Antonio Damato ◽

Mariateresa Ambrosio ◽

...

Keyword(s):

Gene Therapy ◽

Endothelial Function ◽

Knockout Mice ◽

Vascular Reactivity ◽

Viral Vector ◽

Intima Media Thickness ◽

Doppler Imaging ◽

Inflammatory Phenotype ◽

Apoe Knockout Mice

Abstract Aims Here, we aimed to determine the therapeutic effect of longevity-associated variant (LAV)-BPIFB4 gene therapy on atherosclerosis. Methods and results ApoE knockout mice (ApoE−/−) fed a high-fat diet were randomly allocated to receive LAV-BPIFB4, wild-type (WT)-BPIFB4, or empty vector via adeno-associated viral vector injection. The primary endpoints of the study were to assess (i) vascular reactivity and (ii) atherosclerotic disease severity, by Echo-Doppler imaging, histology and ultrastructural analysis. Moreover, we assessed the capacity of the LAV-BPIFB4 protein to shift monocyte-derived macrophages of atherosclerotic mice and patients towards an anti-inflammatory phenotype. LAV-BPIFB4 gene therapy rescued endothelial function of mesenteric and femoral arteries from ApoE−/− mice; this effect was blunted by AMD3100, a CXC chemokine receptor type 4 (CXCR4) inhibitor. LAV-BPIFB4-treated mice showed a CXCR4-mediated shift in the balance between Ly6Chigh/Ly6Clow monocytes and M2/M1 macrophages, along with decreased T cell proliferation and elevated circulating levels of interleukins IL-23 and IL-27. In vitro conditioning with LAV-BPIFB4 protein of macrophages from atherosclerotic patients resulted in a CXCR4-dependent M2 polarization phenotype. Furthermore, LAV-BPIFB4 treatment of arteries explanted from atherosclerotic patients increased the release of atheroprotective IL-33, while inhibiting the release of pro-inflammatory IL-1β, inducing endothelial nitric oxide synthase phosphorylation and restoring endothelial function. Finally, significantly lower plasma BPIFB4 was detected in patients with pathological carotid stenosis (>25%) and intima media thickness >2 mm. Conclusion Transfer of the LAV of BPIFB4 reduces the atherogenic process and skews macrophages towards an M2-resolving phenotype through modulation of CXCR4, thus opening up novel therapeutic possibilities in cardiovascular disease.

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