Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation.

Aims: The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease.

Methods And Results: Interleukin-6-overexpressing (IL-6) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6 mice) overexpressing the cytokine in myeloid cells.

Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation.

Psoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17A , IL-17A control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin-/luminol-based assays, respectively.

Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction.

Aims: Traffic noise may play an important role in the development and deterioration of ischaemic heart disease. Thus, we sought to determine the mechanisms of cardiovascular dysfunction and inflammation induced by aircraft noise in a mouse model of myocardial infarction (MI) and in humans with incident MI.

Methods And Results: C57BL/6J mice were exposed to noise alone (average sound pressure level 72 dB; peak level 85 dB) for up to 4 days, resulting in pro-inflammatory aortic gene expression in the myeloid cell adhesion/diapedesis pathways.

B lymphocyte-deficiency in mice promotes venous thrombosis.

Cells of the innate immune system, including monocytes and neutrophils, are key players in the process of venous thrombosis. T lymphocytes have recently been implicated in venous thrombus resolution but the role of B lymphocytes in thrombosis is unknown. The present study was conducted to address this question using a mouse model of partial ligation of the inferior vena cava.

Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure.

Background: Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis.

Alpha-2-macroglobulin in hemostasis and thrombosis: An underestimated old double-edged sword.

Antiproteinases such as alpha-2-macroglobulin (A2M) play a role in hemostasis. A2M is highly conserved throughout evolution and is a high molecular weight homo-tetrameric glycoprotein. A2M proteinase inhibitor activity is possible via a unique cage structure leading to proteinase entrapment without direct enzymatic activity inhibition.

Effects of Dietary Protein Intake on Cutaneous and Systemic Inflammation in Mice with Acute Experimental Psoriasis.

Background: Psoriasis is a systemic inflammatory disorder, primarily characterized by skin plaques. It is linked to co-morbidities including cardiovascular disease and metabolic syndrome. Several studies demonstrate that dietary habits can influence psoriasis development and severity.

Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect.

Aim: Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi-organ metabolic adjustments to prevent dehydration. Here, we tested the hypothesis that chronic water loss across diseased skin leads to similar adaptive water conservation responses as observed in experimental renal failure or high salt diet.

Methods: We studied mice with keratinocyte-specific overexpression of IL-17A which develop severe psoriasis-like skin disease.

Nox2+ myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1.

Aims: Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI.

Methods And Results: HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending coronary artery.

Stabilization of Perivascular Mast Cells by Endothelial CNP (C-Type Natriuretic Peptide).

Objective: Activated perivascular mast cells (MCs) participate in different cardiovascular diseases. Many factors provoking MC degranulation have been described, while physiological counterregulators are barely known. Endothelial CNP (C-type natriuretic peptide) participates in the maintenance of vascular barrier integrity, but the target cells and mechanisms are unclear.

Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation.

Background: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease.

Lack of T-bet reduces monocytic interleukin-12 formation and accelerates thrombus resolution in deep vein thrombosis.

The role of leukocytes in deep vein thrombosis (DVT) resolution is incompletely understood. We determined how depletion of lysozyme positive (LysM) cells and a switched-off type 1 immune response influences thrombus resolution. DVT was induced in 12-week-old male mice by inferior vena cava (IVC) stenosis.