• Diospyros digyna Jacq.
• antioxidants
• bioactive compounds
• cellular senescence
• endothelial progenitor cells

• dyslipidemia
• endothelial function
• high-density lipoprotein cholesterol
• low-density lipoprotein cholesterol
• triglycerides

• Humans
• Triglycerides
• Cholesterol, HDL
• Cholesterol, LDL
• Dyslipidemias
• Atherosclerosis/complications

• cellular senescence
• chronic inflammation
• endothelial dysfunction
• inflamm-ageing
• vascular alterations

• Humans
• Vascular Diseases/metabolism
• Inflammation/metabolism
• Cellular Senescence

Compared to clopidogrel, prasugrel has a lower incidence of ischemic events following percutaneous coronary intervention (PCI) because of an early reduction during the acute phase in P2Y12 reaction units (PRU). The objective of this study was to compare the antiplatelet effect and vascular endothelial function of both drugs during the chronic phase after PCI. Patients who had undergone PCI and were confirmed to have no restenosis by follow-up coronary angiography under dual anti-platelet therapy with clopidogrel (75 mg/day) and aspirin (100 mg/day) were randomized to either continue clopidogrel or switch to prasugrel (3.75 mg/day). At baseline, prior to randomization we determined the CYP2C19 genotype. At the baseline and 24 weeks after randomization, the P2Y12 reactivity unit (PRU) was measured using the VerifyNow™ P2Y12 assay. Endothelial function was evaluated by flow-mediated vasodilation (FMD) and reactive hyperemia peripheral arterial tonometry (RH-PAT), while and circulating CD34+/CD133+/CD45^low progenitor cells were measured by flow cytometric analysis. Serum high-sensitivity C-reactive protein (hsCRP) level was also measured. The PRU was reduced significantly in the prasugrel group (P = 0.0008), especially in patients who were intermediate or poor metabolizers based on the CYP2C19 genotype (P < 0.0001). This reduction was not observed in the clopidogrel group. The number of CD34+/CD133+/CD45^low cells increased in the clopidogrel group (P = 0.008), but not in the prasugrel group. The hsCRP, FMD and reactive hyperemia index measured by RH-PAT did not change in either group. Prasugrel is potentially better than clopidogrel for preventing thrombotic events, although clopidogrel may have an advantage over prasugrel in terms of preventing atherosclerotic events. Proper use of thienopyridine drugs based on the CYP2C19 genotype has promising clinical potential.

• Clopidogrel
• Coronary artery disease
• Endothelial progenitor cell
• Platelet reactivity
• Prasugrel

Behçet's syndrome (BS) is a systemic vasculitis considered as the prototype of a systemic inflammation-induced thrombotic condition whose pathogenesis cannot be explained just by coagulation abnormalities. Circulating hematopoietic progenitor cells (CPC), a population of rare, pre-differentiated adult stem cells originating in the bone marrow and capable of both self-renewal and multi-lineage differentiation, are mobilized in response to vascular injury and play a key role in tissue repair. In cardiovascular and thrombotic diseases, low circulating CPC number and reduced CPC function have been observed. Oxidative stress may be one of the relevant culprits that account for the dysfunctional and numerically reduced CPC in these conditions. However, the detailed mechanisms underlying CPC number reduction are unknown. On this background, the present study was designed to evaluate for the first time the possible relationship between CPC dysfunction and oxidative stress in BS patients. In BS patients, we found signs of plasma oxidative stress and significantly lower CD34+/CD45^−/dim and CD34+/CD45^−/dim/CD133+ CPC levels. Importantly, in all the considered CPC subsets, significantly higher ROS levels with respect to controls were observed. Higher levels of caspase-3 activity in all the considered CPC population and a strong reduction in GSH content in CPC subpopulation from BS patients with respect to controls were also observed. Interestingly, in BS patients, ROS significantly correlated with CPC number and CPC caspase-3 activity and CPC GSH content significantly correlated with CPC number, in all CPC subsets. Collectively, these data demonstrate for the first time that CPC from BS patients show signs of oxidative stress and apoptosis and that a reduced CPC number is present in BS patients with respect to controls. Interestingly, we observed an inverse correlation between circulating CPC number and CPC ROS production, suggesting a possible toxic ROS effect on CPC in BS patients. The significant correlations between ROS production/GSH content and caspase-3 activity point out that oxidative stress can represent a determinant in the onset of apoptosis in CPC. These data support the hypothesis that oxidative-stress-mediated CPC dysfunctioning may counteract their vascular repair actions, thereby contributing to the pathogenesis and the progression of vascular disease in BS.

• Behçet's syndrome
• apoptosis
• circulating progenitor cells
• oxidation
• thrombosis

• Endothelial progenitor cell
• Lymphangiogenesis
• Neovascularization
• Oral cancer

The tissue kallikrein-kinin system (KKS) is an endogenous multiprotein metabolic cascade which is implicated in the homeostasis of the cardiovascular, renal and central nervous system. Human tissue kallikrein (KLK1) is a serine protease, component of the KKS that has been demonstrated to exert pleiotropic beneficial effects in protection from tissue injury through its anti-inflammatory, anti-apoptotic, anti-fibrotic and anti-oxidative actions. Mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs) constitute populations of well-characterized, readily obtainable multipotent cells with special immunomodulatory, migratory and paracrine properties rendering them appealing potential therapeutics in experimental animal models of various diseases. Genetic modification enhances their inherent properties. MSCs or EPCs are competent cellular vehicles for drug and/or gene delivery in the targeted treatment of diseases. KLK1 gene delivery using adenoviral vectors or KLK1 protein infusion into injured tissues of animal models has provided particularly encouraging results in attenuating or reversing myocardial, renal and cerebrovascular ischemic phenotype and tissue damage, thus paving the way for the administration of genetically modified MSCs or EPCs with the human tissue KLK1 gene. Engraftment of KLK1-modified MSCs and/or KLK1-modified EPCs resulted in advanced beneficial outcome regarding heart and kidney protection and recovery from ischemic insults. Collectively, findings from pre-clinical studies raise the possibility that tissue KLK1 may be a novel future therapeutic target in the treatment of a wide range of cardiovascular, cerebrovascular and renal disorders.

• Biomarkers
• Cardiovascular disease
• Circulating progenitor cells
• Oncoming diseases
• Predictors

• Animals
• Cardiomyopathies/therapy
• Clinical Trials as Topic
• Humans
• Stem Cell Transplantation/methods
• Stem Cell Transplantation/trends
• Stem Cells/cytology

• Aging
• CD34+ progenitor cells
• Hematopoietic progenitor cells
• Hypertension
• Lercanidipine

• Aged
• Antigens, CD34
• Antihypertensive Agents/therapeutic use
• Blood Pressure/drug effects
• Dihydropyridines/therapeutic use
• Female
• Flow Cytometry
• Hematopoietic Stem Cells/drug effects
• Humans
• Hypertension/drug therapy
• Male
• Middle Aged

• Endothelial progenitor cell
• Neovascularization
• Oral cancer
• Tumorigenesis

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are used to reduce cholesterol biosynthesis in the liver. Accordingly, statins regulate nitric oxide (NO) and glutamate metabolism, inflammation, angiogenesis, immunity and endothelial progenitor cells (EPCs) functions. The function of EPCs are regulated by stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β), etc. Even though the pharmacologic mechanisms by which statins affect the neovasculogenesis of circulating EPCs, it is still unknown whether statins affect the EPCs function through the regulation of CXCR4, a SDF-1 receptor expression. Therefore, we desired to explore the effects of statins on CXCR4 expression in EPC-mediated neovascularization by in vitro and in vivo analyses. In animal studies, we analyzed the effects of atorvastatin or rosuvastatin treatments in recovery of capillary density and blood flow, the expression of vWF and CXCR4 at ischemia sites in hindlimb ischemia ICR mice. Additionally, we analyzed whether the atorvastatin or rosuvastatin treatments increased the mobilization, homing, and CXCR4 expression of EPCs in hindlimb ischemia ICR mice that underwent bone marrow transplantation. The results indicated that statins treatment led to significantly more CXCR4-positive endothelial progenitor cells incorporated into ischemic sites and in the blood compared with control mice. In vivo, we isolated human EPCs and analyzed the effect of statins treatment on the vasculogenic ability of EPCs and the expression of CXCR4. Compared with the control groups, the neovascularization ability of EPCs was significantly improved in the atorvastatin or rosuvastatin group; this improvement was dependent on CXCR4 up-regulation. The efficacy of statins on improving EPC neovascularization was related to the SDF-1α/CXCR4 axis and might be regulated by the NO. In conclusion, atorvastatin and rosuvastatin improved neovascularization in hindlimb ischemia mice; this effect may have been mediated by increased CXCR4 expression in EPCs.

• Endothelial protection
• HPLC-Q-TOF-MS/MS
• HUVECs extraction
• Schisandrin
• YiQiFuMai Powder Injection

Although autologous bone marrow cell (BMC) therapy has emerged as a promising treatment for acute myocardial infarction (AMI), trials reported mixed results. In the BONAMI trial, active smoking reduced cardiac function recovery after reperfused AMI. Therefore, we hypothesized that variability in the functionality of BMCs retrieved from patients with cardiovascular risk factors may partly explain these mixed results. We investigated the characteristics of progenitor cells in active smokers and non-smokers with AMI and their potential impact on BMC therapy efficacy.

Bone marrow and blood samples from 54 smoking and 47 non-smoking patients enrolled in the BONAMI cell therapy trial were analyzed.

The white BMC and CD45dimCD34+ cell numbers were higher in active smokers (P = 0.001, P = 0.03, respectively). In marked contrast, either bone marrow or blood endothelial progenitor CD45dimCD34 + KDR + cells (EPCs) were decreased in active smokers (P = 0.005, P = 0.04, respectively). Importantly, a multivariate analysis including cardiovascular risk factors confirmed the association between active smoking and lower EPC number in bone marrow (P = 0.04) and blood (P = 0.04). Furthermore, baseline circulating EPC count predicted infarct size decrease at three months post-AMI in non-smokers (P = 0.01) but not in active smokers. Interestingly, baseline circulating EPCs were no longer predictive of cardiac function improvement in the BMC therapy group.

These data suggest that circulating EPCs play an important role in cardiac repair post-AMI only in non-smokers and that active smoking-associated EPC alterations may participate in the impairment of cardiac function recovery observed in smokers after AMI, an effect that was overridden by BMC therapy.

The tissue kallikrein-kinin system exerts a wide spectrum of biological activities in the cardiovascular, renal and central nervous systems. Tissue kallikrein-kinin modulates the proliferation, viability, mobility and functional activity of certain stem cell populations, namely mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), mononuclear cell subsets and neural stem cells. Stimulation of these stem cells by tissue kallikrein-kinin may lead to protection against renal, cardiovascular and neural damage by inhibiting apoptosis, inflammation, fibrosis and oxidative stress and promoting neovascularization. Moreover, MSCs and EPCs genetically modified with tissue kallikrein are resistant to hypoxia- and oxidative stress-induced apoptosis, and offer enhanced protective actions in animal models of heart and kidney injury and hindlimb ischemia. In addition, activation of the plasma kallikrein-kinin system promotes EPC recruitment to the inflamed synovium of arthritic rats. Conversely, cleaved high molecular weight kininogen, a product of plasma kallikrein, reduces the viability and vasculogenic activity of EPCs. Therefore, kallikrein-kinin provides a new approach in enhancing the efficacy of stem cell therapy for human diseases.

• Tissue kallikrein
• Plasma kallikrein
• Kinin
• Mesenchymal stem cells
• Endothelial progenitor cells
• Neural stem cells
• Heart
• Kidney
• Brain

• R01 HL029397 NHLBI NIH HHS
• R01 HL044083 NHLBI NIH HHS
• R01 HL118516 NHLBI NIH HHS

Kallistatin exerts pleiotropic activities in inhibiting inflammation, apoptosis, and oxidative stress in endothelial cells. Because endothelial progenitor cells (EPCs) play a significant role in vascular repair, we investigated whether kallistatin contributes to vascular regeneration by enhancing EPC migration and function.

We examined the effect of endogenous kallistatin on circulating EPCs in a rat model of vascular injury and the mechanisms of kallistatin on EPC mobility and function in vitro. In deoxycorticosterone acetate–salt hypertensive rats, we found that kallistatin depletion augmented glomerular endothelial cell loss and diminished circulating EPC number, whereas kallistatin gene delivery increased EPC levels. In cultured EPCs, kallistatin significantly reduced tumor necrosis factor‐α–induced apoptosis and caspase‐3 activity, but kallistatin's effects were blocked by phosphoinositide 3‐kinase inhibitor (LY294002) and nitric oxide (NO) synthase inhibitor (l‐NAME). Kallistatin stimulated the proliferation, migration, adhesion and tube formation of EPCs; however, kallistatin's actions were abolished by LY294002, l‐NAME, endothelial NO synthase–small interfering RNA, constitutively active glycogen synthase kinase‐3β, or vascular endothelial growth factor antibody. Kallistatin also increased Akt, glycogen synthase kinase‐3β, and endothelial NO synthase phosphorylation; endothelial NO synthase, vascular endothelial growth factor, and matrix metalloproteinase‐2 synthesis and activity; and NO and vascular endothelial growth factor levels. Kallistatin's actions on phosphoinositide 3‐kinase–Akt signaling were blocked by LY294002, l‐NAME, and anti–vascular endothelial growth factor antibody.

Endogenous kallistatin plays a novel role in protection against vascular injury in hypertensive rats by promoting the mobility, viability, and vasculogenic capacity of EPCs via enhancing NO and vascular endothelial growth factor levels through activation of phosphoinositide 3‐kinase–Akt signaling. Kallistatin therapy may be a promising approach in the treatment of vascular diseases.

• angiogenesis
• apoptosis
• endothelial progenitor cells
• kallistatin
• nitric oxide

Royal College of Surgeons (RCS) rats develop vasculopathy as photoreceptors degenerate. The aim of this study was to examine the effect of erythropoietin (EPO) on retinopathy in RCS rats.

Fluorescein angiography was used to monitor retinal vascular changes over time. Changes in retinal glia and vasculature were studied by immunostaining. To study the effects of EPO on retinal pathology, EPO (5000 IU/kg) was injected intraperitoneally in 14 week old normal and RCS rats twice a week for 4 weeks. Changes in the retinal vasculature, glia and microglia, photoreceptor apoptosis, differential expression of p75 neurotrophin receptor (p75^NTR), pro-neurotrophin 3 (pro-NT3), tumour necrosis factor-α (TNFα), pigment epithelium derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A), the production of CD34⁺ cells and mobilization of CD34⁺/VEGF-R2⁺ cells as well as recruitment of CD34⁺ cells into the retina were examined after EPO treatment.

RCS rats developed progressive capillary dropout and subretinal neovascularization which were accompanied by retinal gliosis. Systemic administration of EPO stabilized the retinal vasculature and inhibited the development of focal vascular lesions. Further studies showed that EPO modulated retinal gliosis, attenuated photoreceptor apoptosis and p75^NTR and pro-NT3 upregulation, promoted the infiltration of ramified microglia and stimulated VEGF-A expression but had little effect on TNFα and PEDF expression. EPO stimulated the production of red and white blood cells and CD34⁺ cells along with effective mobilization of CD34⁺/VEGF-R2⁺ cells. Immunofluorescence study demonstrated that EPO enhanced the recruitment of CD34⁺ cells into the retina.

Our results suggest that EPO has therapeutic potentials in treatment of neuronal and vascular pathology in retinal disease. The protective effects of EPO on photoreceptors and the retinal vasculature may involve multiple mechanisms including regulation of retinal glia and microglia, inhibition of p75^NTR-pro-NT3 signaling together with stimulation of production and mobilization of bone marrow derived cells.

The number and function of endothelial progenitor cells (EPCs) may be a predictive factor for the severity and outcome of cardiovascular disease. However, the manipulation of bone marrow mononuclear cell (BMMC) cultures for EPCs is an elaborate and difficult procedure in small experimental animals. The present study aimed to assess the feasibility of whole bone marrow cell (WBMC) culture for expanding EPCs in small experimental animals. C57BL/6 mice (age, 3–4 weeks; weight, 9.47±0.76 g) were used as the experimental animals, and WBMCs were isolated from the femora and tibiae and cultured in endothelial cell growth medium-2. A BMMC culture for EPCs was used as a control. EPC growth, phenotype and functions were assessed in vitro and in vivo. The results demonstrated that EPCs were easily obtained from a WBMC culture in vitro. The cells exhibited similar growth and biological characteristics when compared with the EPCs derived from the traditional BMMC culture system. Thus, the cells were able to simultaneously bind to lectin and cause phagocytosis of acetylated-low density lipoproteins. In addition, the cells exhibited high expression levels of cluster of differentiation 34 and fetal liver kinase 1, and possessed similar functional properties to BMMC-derived EPCs, including vascular network formation, proliferation, adhesion and migration abilities in vitro. Thus, WBMC-derived EPCs can improve the outcome of pulmonary vascular disease when transplanted into a monocrotaline-induced pulmonary hypertension mouse model. The results of the present study indicated that the WBMC culture system is a more convenient and effective method of obtaining and expanding EPCs compared with BMMC culture, with the advantage of a simplified procedure.

• bone marrow
• endothelial progenitor cells
• model
• mouse

• continuous positive airway pressure adherence
• intermittent hypoxia
• oxidative stress
• sympathetic activation
• systemic inflammation

• Cell separation
• Controlled growth factors release
• Endothelial progenitor cells
• Magnetic nanoparticles
• Thermo-responsive polymers

• Chemoembolization, Therapeutic/methods
• Chemoembolization, Therapeutic/trends
• Female
• Forecasting
• Genetic Therapy/methods
• Genetic Therapy/trends
• Humans
• Male
• Molecular Targeted Therapy/methods
• Molecular Targeted Therapy/trends
• Nanotechnology/methods
• Photochemotherapy/methods
• Photochemotherapy/trends
• Radiography, Interventional/methods
• Radiography, Interventional/trends
• Sensitivity and Specificity

Stem/progenitor cell-based therapy has successfully been used as a novel therapeutic strategy for vascular diseases triggered by endothelial dysfunction. The aim of this study was to investigate the effects of mononuclear cell (MNC) therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE^-/-) mouse.

Spleen-derived MNCs were isolated from green fluorescent protein (GFP)-transgenic mice for cell treatment. A cuff-induced thrombus model was produced by placing a nonconstrictive silastic collar around the left common carotid artery in 20-week-old female apoE^-/- mice. After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff-MNC) or vehicle (Cuff-Vehicle) and were compared with sham-operated animals (Sham).

The histological analysis showed that the MNC treatment reverted occlusive thrombus formation compared to the vehicle and the vessel lumen area to that observed in the Sham group (MNC, 50 ± 4; Vehicle, 20 ± 4; Sham, 55 ± 2 x10³ μm²; p < 0.01). The animals that underwent the carotid cuff placement developed compensatory vessel enlargement, which was reduced by the MNC therapy. In addition, the treatment was able to reduce superoxide anion production, which likely contributed to the reduced apoptosis that was observed. Lastly, the immunofluorescence analysis revealed the presence of endothelial progenitor cells (EPCs) in the carotid endothelia of the apoE^-/- mice.

In situ short-term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid arteries of apoE^-/- mice, possibly through the homing of EPCs, reduction of oxidative stress and decreased apoptosis.

• Animals
• Anticoagulants/pharmacology
• Cell Differentiation/drug effects
• Cells, Cultured
• Endothelial Cells/cytology
• Endothelial Cells/drug effects
• Endothelial Cells/physiology
• Fondaparinux
• Heparin, Low-Molecular-Weight/pharmacology
• Humans
• Mice
• Neovascularization, Physiologic/drug effects
• Neovascularization, Physiologic/physiology
• Polysaccharides/pharmacology
• Stem Cells/cytology
• Stem Cells/drug effects
• Stem Cells/physiology

• Animals
• Anticarcinogenic Agents/adverse effects
• Anticarcinogenic Agents/chemistry
• Anticarcinogenic Agents/pharmacokinetics
• Anticarcinogenic Agents/pharmacology
• Anticarcinogenic Agents/therapeutic use
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacokinetics
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Drug Interactions
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/prevention & control

Recent studies have highlighted the potential of cell therapy for atherosclerosis. The aim of this study was to evaluate the effects of mononuclear cell (MNC) therapy on the development of atherosclerotic lesions in the apolipoprotein E knockout (apoE KO) mouse.

We investigated vascular lipid deposition, vascular remodeling, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in apoE KO mice treated with spleen MNCs isolated from lacZ transgenic mice (apoE KO-MNC) for 8 weeks compared to untreated control mice (apoE KO).

Histological analysis of aortas showed a significant reduction in the lipid deposition area in apoE KO-MNC mice compared to apoE KO mice (0.051 ± 0.004 vs 0.117 ± 0.016 mm², respectively, p < 0.01). In addition, vessel morphometry revealed that MNC therapy prevented the outward (positive) remodeling in apoE KO mice that is normally observed (apoE KO-MNC: 0.98 ± 0.07 vs apoE KO: 1.37 ± 0.09), using wild-type mice (C57BL/6J) as a reference. ApoE KO-MNC mice also have reduced production of superoxide anions and increased eNOS expression compared to apoE KO mice. Finally, immunohistochemistry analysis revealed a homing of endothelial progenitor cells (EPCs) in the aortas of apoE KO-MNC mice.

MNC therapy attenuates the progression of atherosclerosis in the aortas of apoE KO mice. Our data provide evidence that the mechanism by which this attenuation occurs includes the homing of EPCs, a decrease in oxidative stress and an upregulation of eNOS expression.

• Angiotensin II/pharmacology
• Animals
• Calcitonin Gene-Related Peptide/metabolism
• Calcitonin Gene-Related Peptide/pharmacology
• Cell Proliferation/drug effects
• Cells, Cultured
• Culture Media, Conditioned
• Endothelial Cells/metabolism
• Human Umbilical Vein Endothelial Cells/metabolism
• Humans
• MAP Kinase Signaling System
• Muscle, Smooth, Vascular/cytology
• Muscle, Smooth, Vascular/drug effects
• Myocytes, Smooth Muscle/drug effects
• NF-kappa B/metabolism
• Proto-Oncogene Proteins c-fos/metabolism
• Proto-Oncogene Proteins c-myc/metabolism
• Rats
• Stem Cells/metabolism

• Blood Cell Count
• Blood Pressure
• C-Reactive Protein/metabolism
• Case-Control Studies
• Chemokine CXCL12/blood
• Child
• Child, Preschool
• Endothelial Cells/physiology
• Endothelium, Vascular/physiopathology
• Female
• Humans
• Male
• Polysomnography
• Reperfusion
• Sleep Apnea, Obstructive/blood
• Sleep Apnea, Obstructive/physiopathology
• Stem Cells

• HL65270 NHLBI NIH HHS

• Adult
• Antigens, CD34/blood
• Endothelial Cells/cytology
• Female
• Flow Cytometry
• Humans
• Monocytes/cytology
• Monocytes/metabolism
• Pilot Projects
• Smoking/adverse effects
• Smoking/blood
• Stem Cells/cytology
• Stem Cells/metabolism

• Angiogenesis Inducing Agents/therapeutic use
• Animals
• Cardiovascular Agents/therapeutic use
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/pathology
• Cardiovascular Diseases/physiopathology
• Cell Differentiation/drug effects
• Cell Proliferation/drug effects
• Endothelial Cells/drug effects
• Endothelial Cells/pathology
• Humans
• Neovascularization, Physiologic/drug effects
• Regeneration/drug effects
• Stem Cells/drug effects
• Stem Cells/pathology

• Acclimatization/physiology
• Adaptation, Psychological/physiology
• Adult
• Aged
• Altitude Sickness/physiopathology
• Altitude Sickness/prevention & control
• Austria
• Blood Pressure Monitoring, Ambulatory
• Cholesterol, LDL/blood
• Electrocardiography, Ambulatory
• Female
• Heart Rate/physiology
• Hematopoietic Stem Cells/physiology
• Humans
• Hypercholesterolemia/physiopathology
• Hypercholesterolemia/rehabilitation
• Hypertension/physiopathology
• Hypertension/rehabilitation
• Leisure Activities
• Male
• Medical Tourism
• Metabolic Syndrome/physiopathology
• Metabolic Syndrome/rehabilitation
• Middle Aged
• Mountaineering/physiology
• Pilot Projects
• Randomized Controlled Trials as Topic
• Reference Values
• Retrospective Studies
• Travel