Background Microvascular dysfunction, serum cytokines and chemokines may play important roles in pathophysiology of coronavirus disease 2019 (COVID-19), especially in severe cases. Methods Patients with COVID-19 underwent non-invasive evaluation of systemic endothelium-dependent microvascular reactivity - using laser Doppler perfusion monitoring in the skin of the forearm - coupled to local thermal hyperemia. Maximal microvascular vasodilatation (44° C thermal plateau phase) was used as endpoint. A multiplex biometric immunoassay was used to assess a panel of 48 serum cytokines and chemokines. Severe COVID-19 (S-COVID) was defined according to WHO criteria, while all other cases of COVID-19 were considered mild to moderate (M-COVID). A group of healthy individuals who tested negative for SARS-CoV-2 served as a control group and was also evaluated with LDPM. Results Thirty-two patients with COVID-19 (25% S-COVID) and 14 controls were included. Basal microvascular flow was similar between M-COVID and controls (P=0.69) but was higher in S-COVID than in controls (P=0.005) and M-COVID patients (P=0.01). The peak microvascular vasodilator response was markedly decreased in both patient groups (M-COVID, P=0.001; S-COVID, P<0.0001) compared to the healthy group. The percent increases in microvascular flow were markedly reduced in both patient groups (M-COVID, P<0.0001; S-COVID, P<0.0001) compared to controls. Patients with S-COVID had markedly higher concentrations of dissimilar proinflammatory cytokines and chemokines, compared to patients with M-COVID. Conclusions In patients with COVID-19, especially with S-COVID, endothelium-dependent microvascular vasodilator responses are reduced, while serum cytokines and chemokines involved in the regulation of vascular function and inflammation are increased.

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ObjectiveEndothelial progenitor cells (EPCs) are produced in the bone marrow and mobilized to the peripheral blood playing a key role in endothelial repair. The objective of this study was to evaluate circulating EPC before and after percutaneous coronary intervention (PCI) with stent implantation and their associations with coronary restenosis and adverse cardiovascular events. Venous blood was obtained before and the day after PCI. Quantification of total white blood count and identification of EPCs (CD45−CD34+CD31+CD133/2+CD309+) through immunophenotyping by flow cytometry was performed. The primary outcome was either restenosis detected by new coronary angiography or angina with myocardial ischemia at the territory of the stented coronary artery. Secondary outcomes were angina without demonstrable myocardial ischemia, acute coronary syndrome or all-cause death.Results37 patients were followed for 1 year. The median EPC count before PCI was 320 cells/mcl and after PCI 286 cells/mcl. A decrease of EPC count was found in 65% of the patients, while 35% displayed an increase. Primary outcomes occurred in 10.8% and the secondary in 37.8% of the patients. Despite a higher level of EPC before (402 cell/mcl) and after PCI (383 cell/mcl) in patients with the secondary outcomes, there was no significant association between EPC and cardiovascular events.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3401-y) contains supplementary material, which is available to authorized users.

This study compared macro‐ and microvascular endothelial function and redox status in active vs inactive HIV‐infected patients (HIVP) under antiretroviral therapy. Using a cross‐sectional design, macro‐ and microvascular reactivity, systemic microvascular density, and oxidative stress were compared between 19 HIVP (53.1 ± 6.1 year) enrolled in a multimodal training program (aerobic, strength and flexibility exercises) for at least 12 months (60‐minutes sessions performed 3 times/wk with moderate intensity) vs 25 sedentary HIVP (51.2 ± 6.3 year). Forearm blood flow during reactive hyperemia (521.7 ± 241.9 vs 361.4% ± 125.0%; P = 0.04) and systemic microvascular density (120.8 ± 21.1 vs 105.6 ± 25.0 capillaries/mm2; P = 0.03) was greater in active than inactive patients. No significant difference between groups was detected for endothelium‐dependent and independent skin microvascular vasodilation (P > 0.05). As for redox status, carbonyl groups (P = 0.22), lipid peroxidation (P = 0.86), catalase activity (P = 0.99), and nitric oxide levels (P = 0.72) were similar across groups. However, superoxide dismutase activity was greater in active vs inactive HIVP (0.118 ± 0.013 vs 0.111 ± 0.007 U/mL; P = 0.05). Immune function reflected by total T CD4 and T CD8 counts (cell/mm3) did not differ between active and inactive groups (P > 0.82). In conclusion, physically active HIVP exhibited similar immune function, but greater macrovascular reactivity, systemic microvascular density, and superoxide dismutase activity than inactive patients of similar age.

The sympathetic nervous system (SNS) plays a fundamental role in the pathophysiology of cardiovascular diseases, including primary arterial hypertension. In this study, we aimed to investigate whether the expression of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and the b 2 -adrenergic receptor (b 2 -AR) in immune cells from peripheral blood, reflect central SNS activity in spontaneously hypertensive rats (SHR). TH expression in the lower brainstem and adrenal glands and b 2 -AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and b 2 -AR expression was evaluated by flow cytometry before and after chronic treatment with the centrally-acting sympathoinhibitory drug clonidine. Western blot analyses showed increased TH and b 2 -AR expression in the lower brainstem and increased TH in adrenal glands from SHR compared to normotensive Wistar Kyoto rats (WKY). Lower brainstem from SHR treated with clonidine presented reduced TH and b 2 -AR levels, and adrenal glands had decreased TH expression compared to SHR treated with vehicle. Flow cytometry showed that the percentage of leukocytes that express b 2 -AR is higher in SHR than in WKY. However, the percentage of leukocytes that expressed TH was higher in WKY than in SHR. Moreover, chronic treatment with clonidine normalized the levels of TH and b 2 -AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and b 2 -AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.

Objective: To evaluate endothelial progenitor cells (EPCs) and systemic microvascular function in patients with severe hypercholesterolemia, comparing patients with the definite familial hypercholesterolemia (FH) phenotype (DFH) or probable/possible FH phenotype (PFH). There is a large spectrum of atherosclerotic disease between these two clinical phenotypes of FH, and to acquire further knowledge of the pathophysiology of vascular disease in both is desirable. Methods: Subjects with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol (LDL-C) >190 mg/dL, were classified as DFH or PFH and underwent measurement of the number of EPCs by flow cytometry and evaluation of cutaneous microvascular reactivity using a laser speckle contrast-imaging system with iontophoresis of acethylcholine (ACh) or sodium nitroprusside. EPCs were defined as CD45- or CD45^low, CD34+CD133+CD309+ cells. Categorical variables were compared using Fisher test and continuous variables with Student t test or Mann-Whitney test, and a value of p < 0.05 was considered statistically significant. Results: Patients with DFH had higher LDL-C than those with PFH. There was no difference in the median number of EPCs between patients with DFH or PFH, but there was a significant reduction of endothelial-dependent, ACh-induced vasodilatation in the former. Conclusion: Patients with DFH have impaired microvascular endothelial-dependent vasodilatation compared to those with PFH, indicating more severe vascular disease in the former.

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Given the limited therapeutic options for refractory dilated cardiomyopathy we decided to perform a phase I clinical trial using bone marrow derived mononuclear cells in patients with functional classes II and IV of the NYHA. Inclusion criteria required EF% (Simpson) <35%, VO2 max < 16 kg.ml /min and signed informed consent. After enrollment patients were subject to the following exams at baseline, 2 and 6 months after cell therapy: 12 lead ECG and 24hs holter, echocardiography, chest X-ray, blood biochemistry, BNP, ergoespirometry, MRI and Minnesota Questionnaire. Patients were subject to bone marrow aspiration (80–100 mL) under sedation and local anesthesia and mononuclear cells were obtained after Ficoll gradient centrifugation. A mean of 198 million cells diluted in 20 ml of saline were slowly delivered through catheterization in the coronary arteries (10 ml in LAD, 5 ml in RC, 5 ml in CX). After the procedure patients remained hospitalized for 48hs. We report the results of the first 22 patients that completed the follow-up period. No adverse effects related to the procedure were observed, nor were arrhythmias detected after cell delivery. Four patients died during follow up. For the 18 patients that completed follow up, there was a significant improvement in NYHA functional class and quality of life at 2 and 6 months (p<0.03 and p< 0.007, respectively). There were no statistically significant changes in EF% (18.6%, 18.6% and 19%), EDV (360, 371, 386 ml) or ESV (295, 308, 314 ml) at baseline, 2 and 6 months respectively as measured by MRI. Maximal oxygen consumption showed as significant increase after cell therapy (12.5, 15.3, 16.8 ml/kg.min), and the number of patients with oxygen consumption below the threshold for cardiac transplantation decrease from 75% at baseline to 25% six months after cell therapy. BNP levels were not significantly altered (650, 475, 530 pg/ml). When observed individually, 4 of the 17 patients examined showed an increase in EF% by MRI ≥5%, 7 did not change EF% and 3 decreased EF% by ≥5%. In conclusion, the procedure is safe and feasible but further studies are necessary to test for efficacy.