Dyslipidemias ; metabolism ; physiopathology ; Endothelium, Vascular ; physiopathology ; Humans

The endothelium plays an important role in maintaining vascular homeostasis, regulating vascular tone and blood flow, and preserving a non-thrombogenic blood-tissue interface, and the normal function of the vascular endothelium is essential for penile erection. In most cases, erectile dysfunction (ED) is accompanied by endothelial dysfunction, and endothelial injury is a major pathological basis of ED, which can be induced by bad lifestyles, cardiovascular diseases, reactive oxygen species, and inflammatory mediators. The vascular endothelium is capable of self-repairing, and endothelial injury results from the unbalanced factors of injury and repair. This review focuses on the mechanism and repair of endothelial injury and the relationship of endothelial injury with ED.
Endothelium, Vascular ; metabolism ; pathology ; Erectile Dysfunction ; metabolism ; pathology ; Humans ; Male

Animals ; Endothelium, Vascular ; Humans ; Lipid Metabolism ; Metabolic Diseases

OBJECTIVETo determine the change of P-selectin in avulsion-injured vessels.

METHODSDifferent stretch forces of 60, 70, 80 and 90 g were applied to a vascular injury model. The expression changes of P-selectin were evaluated by RT-PCR.

RESULTSThe expression of P-selection mRNA in the injured vessels increased with the stretch force.

CONCLUSIONThe result associated with our previous study indicated that P-selectin may be involved in thrombosis.

Animals ; Endothelium, Vascular ; P-Selectin ; metabolism ; RNA, Messenger ; metabolism ; Vascular System Injuries ; genetics ; metabolism

OBJECTIVETo investigate the effect of antisense KLF4 (Krüppel-like factor 4) gene on the expression of vWF and PAI-1 in endothelial cells.

METHODSHuman umbilical vein endothelial cells (HUVEC) were isolated from umbilical vein and cultured in endothelial cell medium. The recombinant adenoviral plasmid carrying the antisense KLF4 gene was constructed by homologous recombination. KLF4, PAI-1 and vWF mRNAs and proteins expression were detected by real time-PCR, Western blot, and confocal laser microscopy.

RESULTSRecombinant adenoviral plasmid carrying the antisense KLF4 gene (Ad-KLF4AS) was constructed successfully. Compared with the control Ad-GFP infection group, Ad-KLF4AS at a 200 MOI can down-regulate the expression of KLF4 gene in HUVEC (from 0.59 ± 0.01 to 0.44 ± 0.06) (P < 0.05), and increase vWF mRNA (from 1.04 ± 0.03 to 1.17 ± 0.05) and protein expression (P < 0.05). PAI-1 mRNA and protein of Ad-KLF4AS infection group was higher than that of Ad-GFP infection group. PAI-1 mRNA between the two groups had no significant difference (P > 0.05).

CONCLUSIONSDown-regulation of KLF4 leads to increase in expression of vWF and PAI-1 in endothelial cells. KLF4 might play an important role in regulation of endothelial coagulant function.

Cells, Cultured ; Down-Regulation ; Endothelial Cells ; metabolism ; Endothelium ; Endothelium, Vascular ; metabolism ; Humans ; Plasminogen Activator Inhibitor 1 ; RNA, Messenger ; genetics

OBJECTIVE: To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models. METHODS: Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested. RESULTS: KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl₂ in Ca²⁺-free solutions containing K⁺ or NE. In addition, KXA pretreatment inhibited accumulation of Ca²⁺ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels. CONCLUSION KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.
Aerosols ; Animals ; Aorta, Thoracic ; Calcium/metabolism* ; Endothelium, Vascular/metabolism* ; Myocardial Ischemia/metabolism* ; Rats ; Vasodilation

In order to further investigate the effect of annexin II (Ann-II) on tissue plasminogen activator (t-PA)-dependent plasminogen (PLG) activation and its interactive mechanism, recombinant native Ann-II bound t-PA, PLG and plasmin with high affinity was examined. The flow cytometric assay showed that the ann-II expression rate was higher in the human umbilical vein endothelial cell (HUVEC) (87.65%) than in the HL-60 cells as controls (35.79%). Two irrelevant proteins, bovine serum albumin (BSA) and equine IgG (EIG) had no effect on the production of plasmin. Ann-II-mediated enhancement of t-PA-dependent PLG activation was inhibited by epsilon-aminocaproic acid or by pretreatment of Ann-II with carboxypeptidase B with the inhibitive rate being 77.8% and 77.0%, respectively. It was revealed that the effect of Ann-II on PLG activation was specific for t-PA. Urokinase didn't bind to Ann-II, demonstrating the role of receptor-related lysine residues on activation of PLG, showing that the Ann-II-PLG interaction was dependent upon carboxyl-terminal lysine residues. These findings suggest that annexin II-mediated co-assembly of t-PA and PLG may promote plasmin generation and play a key role in modulating fibrinolysis on the endothelial surface.
Annexin A2/*pharmacology ; Cells, Cultured ; Endothelium, Vascular/cytology ; Endothelium, Vascular/*metabolism ; Fibrinolysis ; Plasminogen/*metabolism ; Recombinant Proteins/pharmacology ; Tissue Plasminogen Activator/*metabolism ; Umbilical Veins/cytology

OBJECTIVETo explore the relationship of inflammation and endothelial dysfunction with risks to cardiovascular disease (CVD).

METHODSBlood pressure, body weight, body height, waist circumference and lifestyle risk factors were measured and studied among 2589 participants in Inner Mongolia of China, and biomarkers of inflammation and endothelial dysfunction including high-sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), and angiotensin II were investigated.

RESULTSSubjects with metabolic risk factors for CVD had higher levels of hsCRP, sE-selectin and sICAM-1 than those without such risk factors (all P<0.05). Levels of all biomarkers positively and significantly increased with aggregation of the metabolic risk factors among the subjects (all P for trend <0.001). Data from the multivariate analysis showed that participants with high levels of hsCRP [odds ratio (OR): 1.96, 95% confidence interval (CI): 1.52-2.53], sE-selectin (OR: 1.35, 95% CI: 1.05-1.72), and angiotensin II (OR: 1.81, 95% CI: 1.40-2.33) were more likely to develop hypertension; participants with high levels of hsCRP (OR: 2.33, 95% CI: 1.85-2.94), sE-selectin (OR: 1.24, 95% CI: 1.00-1.54), and sICAM-1 (OR: 1.70, 95% CI: 1.30-2.22) were more likely to develop dyslipidemia, and those with high levels of hsCRP (OR: 2.95, 95% CI: 2.27-3.83) and sICAM-1(OR: 2.80, 95% CI: 2.06-3.80) were more likely to develop hyperglycemia.

CONCLUSIONBiomarkers of inflammation and endothelial dysfunction were separately associated with relevant metabolic risk factors for CVD. And appropriate measures should be taken to control inflammation and improve endothelial function among individuals with different metabolic risk factors for CVD.

Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Cardiovascular Diseases ; China ; Endothelium, Vascular ; metabolism ; Humans ; Inflammation

OBJECTIVE: The endothelial glycocalyx (eGC) is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium, which is largely underappreciated. It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries. This study aimed to explore the role of the eGC in various pathologic and physiologic conditions, by reviewing the basic research findings pertaining to the detection of the eGC and its clinical significance. We also explored different pharmacologic agents used to protect and rebuild the eGC. DATA SOURCES: An in-depth search was performed in the PubMed database, focusing on research published after 2003 with keywords including eGC, permeability, glycocalyx and injuries, and glycocalyx protection. STUDY SELECTION: Several authoritative reviews and original studies were identified and reviewed to summarize the characteristics of the eGC under physiologic and pathologic conditions as well as the detection and protection of the eGC. RESULTS: The eGC degradation is closely associated with pathophysiologic changes such as vascular permeability, edema formation, mechanotransduction, and clotting cascade, together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation (sepsis and trauma), ischemia-reperfusion injury, shock, hypervolemia, hypertension, hyperglycemia, and high Na as well as diabetes and atherosclerosis. Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications. CONCLUSIONS Disturbance of the eGC usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC. The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.
Animals ; Databases, Factual ; Endothelium, Vascular ; metabolism ; pathology ; Glycocalyx ; metabolism ; pathology ; Humans ; Shear Strength

OBJECTIVESTo explore the effect of acute smoking on vascular endothelial function, arterial stiffness and the possible underlying mechanisms.

METHODSWe measured the endothelial function and arterial stiffness in 50 healthy chronic smokers before and after acute smoking with EndoPAT2000. The test was carried out on two separate finger tips. The endothelial function was evaluated by PAT ratio of the finger tip and systemic arterial stiffness was evaluated by augmentation index (AI). Plasma soluble intercellular adhesion molecule-1 (sICAM-1) and tissue plasminogen activator (tPA) before and 20 min after acute smoking were measured with enzyme linked immuno sorbent assay.

RESULTSThe PAT ratio was decreased (1.87 ± 0.40 vs. 1.73 ± 0.28, P = 0.004) while AI was significantly increased after acute smoking (2.94% ± 21.77% vs. 7.11% ± 20.65%, P = 0.01). There was no significant changes in sICAM [(306.5 ± 76.1) µg/L vs. (315.7 ± 90.9) µg/L, P = 0.402], but tPA [7.87 (5.41 - 10.08) µg/L vs. 5.77 (3.77 - 9.68) µg/L, P < 0.01] was significantly decreased after smoking.

CONCLUSIONSSmoking could acutely affect endothelia function, arterial stiffness and deteriorate the activity of fibrinolytic system which could lead to coronary thrombosis in smokers.

Adult ; Arteries ; physiopathology ; Elasticity ; Endothelium ; metabolism ; Endothelium, Vascular ; metabolism ; physiopathology ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Middle Aged ; Smoking ; adverse effects ; Tissue Plasminogen Activator ; blood ; Vascular Resistance