CD51/CD61+ Endothelial Microparticles Decrease in Diabetes Patients with Hypertension

Backgrounds: Type 2 Diabetes Mellitus (T2DM) and hypertension are commonly co-occurred and both diseases are related to endothelial dysfunction. Endothelial microparticles (EMPs) are shed from endothelial cells and can be found in condition of endothelial dysfunction. This study aimed to evaluate the circulating endothelial MPs (CD51/CD61+) levels in T2DM patients with or without hypertension and the correlation between endothelial MPs and clinical parameters. Methods and Results: 20 healthy control, 16 T2DM patients without hypertension and 11 T2DM patients with hypertension were recruited. CD51/CD61+ EMPs from all subjects were analyzed by flow cytometry. We found that, in the group of T2DM patients with hypertension, the absolute median number of CD51/CD61+EMPs was significantly decreased, compared with that in the healthy control and T2DM without hypertension groups. Furthermore, we conducted receiver operating characteristics (ROC) analysis to examine the accuracy of CD51/CD61+EMPs in the discrimination  between T2DM patients with hypertension and healthy control, showing the accuracy was 76.4%. In addition, we also found that the accuracy of CD51/CD61+EMPs was 83.5% in the discrimination between T2DM patients with hypertension or without hypertension Conclusion: These findings identify CD51/CD61+EMPs as a potential biomarker to monitor endothelial dysfunction in T2DM patients with hypertension

Endothelial Cells Promote Calcification in Aortic Smooth Muscle Cells from Spontaneously Hypertensive Rats

Background/Aims: Vascular calcification and hypertension are intimately linked, and the progression of hypertension is closely correlated with endothelial dysfunction. However, the role of endothelial cells (ECs) in vascular calcification of hypertension remains unclear. Therefore, the present study explored the effects of ECs on calcification of smooth muscle cells (SMCs) from aortas of spontaneously hypertensive rats (SHR). Methods: Aortic ECs and SMCs were isolated from SHR and Wistar rats, respectively. The roles of ECs in the regulation of SMCs calcification were investigated by co-culture and conditioned culture model. Calcium deposition of SMCs was detected by von Kossa staining. Quantization of calcium content in SMCs was determined colorimetrically by the o-cresolphthalein complexone method. Alkaline phosphatase (ALP) activity was measured colorimetrically by p-nitrophenol. The expression levels of MMP-2, MMP-9 and the calcification-promoting proteins were analyzed by Western blot. Results: Calcium deposition, ALP activity and the expression levels of calcification-promoting proteins in SMCs of SHR were significantly higher than that cultured without ECs after 6 days of co-culture with ECs or conditioned culture with the medium of ECs, however, there were no statistical differences between SMCs of Wistar rats. MMP-2 and MMP-9 in co-cultured ECs from SHR were dramatically higher than that cultured without SMCs, nevertheless, there were no statistical differences between ECs from Wistar rats and between SMCs from SHR or Wistar rats. Moreover, SB-3CT, a specific inhibitor of gelatinases, decreased calcium content and the expression levels of calcification-promoting proteins in both co-cultured and conditionally cultured SMCs from SHR. Conclusion: ECs have the ability to promote calcification of aortic SMCs of SHR, and elevated expressions of MMP-2 and MMP-9 in ECs of SHR might facilitate the calcification of SMCs

Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice

Spinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI, but many problems and risks have not been resolved. Some studies have reported that the therapeutic effect of MSCs on SCI is related to the paracrine secretion of cells. The exosomes secreted by MSCs have therapeutic potential for many diseases. There are abundant pericytes which possess the characteristics of stem cells in the neurovascular unit. Due to the close relationship between pericytes and endothelial cells, the exosomes of pericytes can be taken up by endothelial cells more easily. There are fewer studies about the therapeutic potential of the exosomes derived from pericytes on SCI now. In this study, exosomes of pericytes were transplanted into the mice with SCI to study the restoration of motor function and explore the underlying mechanism. We found that the exosomes derived from pericytes could reduce pathological changes, improve the motor function, the blood flow and oxygen deficiency after SCI. In addition, the exosomes could improve the endothelial ability to regulate blood flow, protect the blood-spinal cord barrier, reduce edema, decrease the expression of HIF-1α, Bax, Aquaporin-4, and MMP2, increase the expression of Claudin-5, bcl-2 and inhibit apoptosis. The experiments in vitro proved that exosomes derived from pericytes could protect the barrier of spinal cord microvascular endothelial cells under hypoxia condition, which was related to PTEN/AKT pathway. In summary, our study showed that exosomes of pericytes had therapeutic prospects for SCI

Changes of Microvascular Vasomotion and Oxygen Metabolism during Cooling and Rewarming Period of Cardiopulmonary Bypass

Microcirculation plays an important role in keeping a stable tissue metabolism during cardiopulmonary bypass (CPB). The relationship between microvascular vasomotion (MV) and total body’s oxygen metabolism with temperature alteration during CPB remains unclear. Is there a relationship, or is the autoregulation a consequence of CO2, pressure and/or blood flow? The purpose of this study was to investigate the effect of temperature alteration on cutaneous MV and the total body’s oxygen metabolism during CPB. Sixteen consecutive patients scheduled for elective cardiac valve replacement surgery were included in this study. The pump flow varied from 1.8–3.0 L/m-2min-1 to maintain venous oxygen saturation above 65% and mean arterial blood pressure above 60 mmHg. At a nasopharyngeal temperature of 30°C, oxygen consumption (VO2) and oxygen extraction (O2 ext) were measured during the cooling and rewarming periods. MV and skin microcircular flow (SMF) were monitored dynamically at the middle of two sides of the eyebrow with a laser Doppler flowmeter simultaneously VO2 and O2 ext at 30°C were significantly lower during the cooling period (VO2, 49.9 ± 17.7 mL/m-2/min-1; O2 ext, 19.3 ± 6.2%) than that during the rewarming period (VO2, 133.3 ± 40.0 mL/ m-2/min-1; O2 ext, 35.2 ± 9.2%) (p .05). SMF and MV were depressed during hypothermic CPB, and there was some recovery during the rewarming period. Compared to baseline, SMF and MV were still significantly reduced during the warming period, indicating microvascular function was abnormal. Some measures should be taken for improvement of microvascular function during CPB

A comparison of the cutaneous microvascular properties of the Spontaneously Hypertensive and the Wistar-Kyoto rats by Spectral analysis of Laser Doppler

This work was aimed to study skin blood perfusion, vasomotion and vascular responses of the Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in different stages of age using spectral. Laser-Doppler flowmetry (LDF) was used to examine the ears and limbs of WKY (12 and 48 weeks old) and SHR (12 and 48 weeks old). The skin blood flow oscillations (SBFOs) were studied by wavelet spectral analysis of LDF tracings. Then, we observed that old groups showed decreased perfusion and SBFO in the ears of both SHR and WKY. The SHR showed obviously lower postocclusive reactive hypera (PORH) ratio at the same age. A decreased peak-time occurred in the SHR of old age group. After PORH test, a statistically significant increase was observed within all subintervals in the absolute amplitude of 12-week WKY and only within IV and III subintervals in the absolute amplitude of 12-week SHR. But, the absolute amplitude of 48-week WKY and SHR showed no statistically significant increase within all subintervals. Results indicated that local regulating function of peripheral vascular was impaired in rat with hypertension and aging. Abbreviations LDF: Laser-Doppler flowmetry; SBF: Skin blood flow; SBFO: Skin blood flow oscillation; PORH: Postocclusive reactive hyperemia; SHR: Spontaneously hypertensive rats; WKY: Wistar-Kyoto rats; LDF: Laser-Doppler flowmetry; LDI: Laser Doppler Imaging; BP: Blood pressure