Editorial: The interplay between oxidative stress, immune cells and inflammation in cardiovascular diseases

Cardiovascular diseases (CVDs) constitute the leading causes of death and reduced quality of life worldwide. Reactive oxygen species (ROS), various immune cells and cytokines participate in crucial signalling pathways implicated in the homeostasis of the cardiovascular system. Dysregulated ROS production and immune system activation have been widely demonstrated to lead to the development of CVDs, hypertension, target organ damage and cardiovascular complications (1, 2). Hypertension is a major risk factor leading to the development of cardiovascular diseases and target organ damage, including hypertensive heart disease. This pathology leads to abnormalities of the heart, involving changes in the structure and function of the left ventricle, the left atrium and coronary arteries. Masenga and Kirabo nicely summarised the current knowledge about hypertensive heart disease, highlighting this cardiac pathology's mechanisms, complications, and implications. In their comprehensive review, published in the current issue, they focused specifically on left ventricular hypertrophy, atrial fibrillation, heart failure, and coronary heart disease, and current and future therapies targeting these complications

T-cell-derived miRNA-214 mediates perivascular fibrosis in hypertension

RATIONALE: Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood. OBJECTIVES: To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening. METHODS AND RESULTS: Out of 381 miRs screened in the perivascular tissues in response to Ang II (angiotensin II)-mediated hypertension, miR-214 showed the highest induction (8-fold, P=0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in perivascular adipose tissue adipocytes. Global deletion of miR-214-/- prevented Ang II-induced periaortic fibrosis, Col1a1, Col3a1, Col5a1, and Tgfib1 expression, hydroxyproline accumulation, and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214-/- mice were protected against endothelial dysfunction, oxidative stress, and increased Nox2, all of which were induced by Ang II in WT mice. Ang II-induced recruitment of T cells into perivascular adipose tissue was abolished in miR-214-/- mice. Adoptive transfer of miR-214-/- T cells into RAG1-/- mice resulted in reduced perivascular fibrosis compared with the effect of WT T cells. Ang II nduced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214-/-. T cell activation, proliferation and chemotaxis pathways were differentially affected. MiR-214-/- prevented Ang II-induction of profibrotic T cell cytokines (IL-17, TNF-a, IL-9, and IFN-y) and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6, and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of patients with hypertension and is directly correlated to pulse wave velocity as a measure of vascular stiffness. CONCLUSIONS: T-cell-derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release

Immune and inflammatory mechanisms in hypertension

Hypertension is a global health problem, with >1.3 billion individuals with high blood pressure worldwide. In this Review, we present an inflammatory paradigm for hypertension, emphasizing the crucial roles of immune cells, cytokines and chemokines in disease initiation and progression. T cells, monocytes, macrophages, dendritic cells, B cells and natural killer cells are all implicated in hypertension. Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow, as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt environment, can contribute to immune activation in hypertension. The activated immune cells migrate to target organs such as arteries (especially the perivascular fat and adventitia), kidneys, the heart and the brain, where they release effector cytokines that elevate blood pressure and cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment and dementia. IL-17 secreted by CD4+ T helper 17 cells and γδ T cells, and interferon-γ and tumour necrosis factor secreted by immunosenescent CD8+ T cells, exert crucial effector roles in hypertension, whereas IL-10 and regulatory T cells are protective. Effector mediators impair nitric oxide bioavailability, leading to endothelial dysfunction and increased vascular contractility. Inflammatory effector mediators also alter renal sodium and water balance and promote renal fibrosis. These mechanisms link hypertension with obesity, autoimmunity, periodontitis and COVID-19. A comprehensive understanding of the immune and inflammatory mechanisms of hypertension is crucial for safely and effectively translating the findings to clinical practice

Wpływ napromieniowania laserem He-Ne oraz kadmu i ołowiu na zmiany w cyklach komórkowych Zea mays L.

The aim of the study was to investigate the effect of red radiation emitted by helium-neon laser (He-Ne) with a wavelength λ = 632.8 nm and trace elements: cadmium (Cd) and lead (Pb), as cadmium nitrate and lead nitrate solutions, at 30 ppm concentrations, on the cell cycle of root-tip meristem cells in maize. Red light stimulated the mitotic activity of the meristemic cells of the maize root-tip meristem growth after irradiation of seed samples with simultaneous treatment in the presence of Cd or Pb. The mitotic index was inhibited when the seeds were treated with distilled water with the addition of Cd or Pb salts. Seeds treated with laser had significantly the highest mitotic index. Results revealed that maize seed pre-treatment with the red light protects the root-tip meristem cells against the mitodepressive effect of Cd and Pb ions. Seed biomodulation using red light emitted by He-Ne laser can positively effect the germination and plant growth

Systemic and vascular inflammation in experimental allergic asthma

Allergic asthma and atherosclerosis are inflammatory diseases characterized by similar sets of circulating inflammatory cells, in addition to mast cells in the airway and vessel wall. Animal models and human studies provide evidence of a potential interaction between the two apparently unrelated diseases. The main objective of this study was to determine whether experimental allergic asthma is accompanied by inflammatory responses, measured as the activation of the vasculature and the presence of immune cells in the perivascular adipose tissue. For this purpose, male Dunkin Hartley guinea pigs weighing 250 - 300 g were sensitized twice with 10 μg ovalbumin dissolved in aluminium hydroxide (Al(OH) ). Allergen inhalation was performed 10 days after the second immunization and continued 5 days a week for 2 months. After that period, T cell and macrophage content was measured by flow cytometry. The aortic expression of inflammatory markers was studied by real-time PCR. The number of T cells in the peripheral blood was significantly greater in the allergic group in comparison to the sham group. We did not find any significant differences in the leukocyte content of the perivascular adipose tissue between the groups. Nor did we identify significant changes in the expression of inflammatory markers (tumor necrosis factor, monocyte chemoattractant protein-1) and adhesion molecules (intercellular adhesion molecules and vascular cell adhesion molecules) in the aorta. Interestingly, we observed a significantly decreased expression of the endothelial nitric oxide synthase (eNOS) mRNA in the aortic vessel of the allergic group compared to the sham group

Local inflammation is associated with aortic thrombus formation in abdominal aortic aneurysms

Intraluminal thrombus formation in aortic abdominal aneurysms (AAA) is associated with adverse clinical prognosis. Interplay between coagulation and inflammation, characterised by leukocyte infiltration and cytokine production, has been implicated in AAA thrombus formation. We studied leukocyte (CD45+) content by flow cytometry in AAA thrombi from 27 patients undergoing surgical repair. Luminal parts of thrombi were leukocyte-rich, while abluminal segments showed low leukocyte content. CD66b+ granulocytes were the most prevalent, but their content was similar to blood. Monocytes (CD14+) and T cells (CD3+) were also abundant, while content of B lymphocytes (CD19+) and NK cells (CD56+CD16+) were low. Thrombi showed comparable content of CD14highCD16– monocytes and lower CD14highCD16+ and CD14dimCD16+, than blood. Monocytes were activated with high CD11b, CD11c and HLA-DR expression. Total T cell content was decreased in AAA thrombus compared to peripheral blood but CD8 and CD3+CD4-CD8– (double negative T cell) contents were increased in thrombi. CD4+ cells were lower but highly activated (high CD69, CD25 and HLA-DR). No differences in T regulatory (CD4+CD25+FoxP3+) cell or pro-atherogenic CD4+CD28null lymphocyte content were observed between thrombi and blood. Thrombus T cells expressed high levels of CCR5 receptor for chemokine RANTES, commonly released from activated platelets. Leukocyte or T cell content in thrombi was not correlated with aneurysm size. However, CD3+ content was significantly associated with smoking in multivariate analysis taking into account major risk factors for atherosclerosis. In conclusion, intraluminal AAA thrombi are highly inflamed, predominantly with granulocytes, CD14highCD16– monocytes and activated T lymphocytes. Smoking is associated with T cell infiltration in AAA intraluminal thrombi

[OP.2D.04] Perivascular T regulatory cells and endothelial dysfunction in human atherosclerosis

No abstract available