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

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

Vascular endothelial growth factor-A (VEGF-A) is a critical angiogenic factor which is mainly secreted from podocytes and epithelial cells in kidney and plays an important role in renal pathophysiology. In recent years, functions of different isoforms of VEGF-A and the new secretion approach via extracellular vesicles (EVs) have been identified. Thus, further understanding are needed for the role of VEGF-A and its isoforms in renal injury and repair. In this review, we summarized the expression, secretion and regulation of VEGF-A, its biological function, and the role of different isoforms of VEGF-A in the development of different renal diseases. Meanwhile, the research progress of VEGF-A as diagnostic marker and therapeutic target for renal diseases were discussed.
Humans ; Kidney/metabolism* ; Kidney Diseases ; Protein Isoforms/metabolism* ; Vascular Endothelial Growth Factor A/physiology*

Vascular endothelial growth factor (VEGF) exerts its biological functions by its specific VEGF receptors (VEGFR), which includes VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1, and neuropilin-2. These VEGFR distributes in endothelial cells, and are also expressed in normal skin, inflammatory skin diseases, and skin cancers. The VEGF-VEGFR signaling pathway may be a new key target in the management of the skin diseases.
Animals ; Humans ; Receptors, Vascular Endothelial Growth Factor ; biosynthesis ; Signal Transduction ; Skin Diseases ; metabolism ; Vascular Endothelial Growth Factor A ; physiology

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.
Angiopoietins ; Endothelial Cells/metabolism* ; Humans ; Lymphatic Diseases ; Lymphatic System/metabolism* ; Receptor, TIE-2/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A

BACKGROUND: Psoriasis is a disease of unknown etiology. Disturbances in lipid metabolism have been suggested as a possible pathogenetic mechanism. OBJECTIVE: The study was performed to investigate the blood lipid, lipoprotein and apolipo-protein levels and their difference according to family history in Korean psoriasis patients. METHODS: Blood samples from seventy three psoriasis patients and twenty three normal persons were measured for total ciolesterol(TC), VLDL-cholesterol(VLDL-C), LDL-cholesterol(LDL-C), HDL-cholesterol(HDL-C), lipoprotein(a) (LPA), triglyceride(TG), apolipoprotein A-I(APO-AI), and apolipoprotein B(AFO-B). Psoriasis patients were divided according to their family history of psoriasis. RESULTS: Compared to ccntrols, TC, LDL-C, LPA, TG, APO-B were significantly elevated in psoriasis patients. Mean varues of LPA and APO-B in psoriasis group were above normal range. VLDL-C were significasitly elevated only in female patients. There was a tendency for psoriasis patients with family history to have higher values than those without family history. CONCLUSION: TC, LDL-C, L,PA, TG, APO-B was increased in psoriasis, especially in the patients with family history, cornpared to control. It is recommended that we must pay attention to the possible risk for the development of cardiac or cerebral vascular disease in psoriasis patients, especially in the presence of family history of psoriasis.
Apolipoproteins ; Apolipoproteins B ; Female ; Humans ; Lipid Metabolism ; Lipoprotein(a) ; Lipoproteins* ; Psoriasis* ; Reference Values ; Vascular Diseases

BACKGROUND: Lipoprotein (a) concentration is mainly determined by apo (a) genotype, but elevated in the atherosclerotic vascular disease more than in normal group with the same apo (a) phenotype. It has been known that Lp (a) has independent metabolism in contrast with other lipoproteins and that the use of cholesterol lowering agent such as HMG-CoA reductase inhibitor for 6 months does not change the level of Lp (a). The results of several studies suggests that Lp (a) may be related to inflammation of atherosclerotic plaque and therefore, long term use of cholesterol lowering agents make plaque stable by reduction of inflammation at plaque. We hypothesized that there is a relationship between long term use of HMG-CoA reductase inhibitor and change of Lp (a) level. We prospectively measured Lp (a), lipids and inflammatory markers before and after long term use of HMG-CoA reductase inhibitor to examine our hypothesis. METHODS: Forty-nine subjects (M:F=28:21, age=59.1+/-12.0) with hyperlipidemia were administered HMG-CoA reductase inhibitor for 15 months (minimum 6 months, maximun 44 months), and Lp (a), lipids and inflammatory markers were measured before and after use of the HMG-CoA reductase inhibitor. In control group (ninty-nine subjects, M:F=60:39, age=61.2+/-9.2), these parameters were measured more than 6 months. RESULTS: In the hyperlipidemia group who were given HMG-CoA reductase inhibitor, baseline levels of total cholesterol, TG, LDL were significantly elevated more than those of the control group, but Lp (a) and inflammatory markers were not significantly different. After use of HMG-CoA reductase inhibitor, the level of Lp (a) was reduced significantly (before 28.9+/-29.3 mg/dl, after 20.0+/-19.0 mg/dl, p=0.009), but not significantly in the control group. There was a minimal relation between baseline Lp (a) levels and percent changes of Lp (a) levels. Total cholesterol and LDL levels reduced significantly after use of the drug, but inflammatory markers did not. CONCLUSION: These data showed that Lp (a) level in the hyperlipidemia group after the long term use of HMG-CoA reductase inhibitor decreased significantly. We suggest that these changes of Lp (a) level may be one of reliable markers for plaque stability in atherosclerotic vascular disease.
Atherosclerosis ; Cholesterol ; Genotype ; Hyperlipidemias ; Inflammation ; Lipoprotein(a) ; Lipoproteins ; Metabolism ; Oxidoreductases* ; Phenotype ; Plaque, Atherosclerotic ; Prospective Studies ; Vascular Diseases

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.
Humans ; Atherosclerosis ; Cardiovascular Diseases ; Endothelium, Vascular ; Homocysteine/metabolism* ; Hyperhomocysteinemia/complications* ; Oxidative Stress ; Risk Factors

OBJECTIVETo investigate Bcl-2/Bax gene expression in different types of carotid plaque, and examine the relationship between gene expression and atherosclerotic plaque instability and the main cause of brain ischemic events.

METHODSTotally 42 human carotid plaque specimens obtained during carotid endarterectomy were divided into stable group (n=19) and unstable group (n=23) based on histopathological studies (HE staining). Eight aortic arteries and their branches from hepatic transplantation donors were taken as control group. Bcl-2/Bax was detected by immunohistochemistry (IHC) staining (n=42) and in situ hybridization (ISH) (n=25, stable 13/unstable 12).

RESULTSBcl-2 gene expression, which was expressed in smooth muscle cells (SMC), endothelial cells (EC), macrophages (MP) and foam cells, was detected in 20 and 9 cases in unstable plaque while 11 and 4 cases in stable plaque by IHC and ISH, respectively (P < 0.05). Bax, which was expressed in SMC and MP, was detected in 18 and 11 cases in unstable plaque, while 8 and 5 cases in stable plaque by IHC and ISH, respectively (P < 0.05).

CONCLUSIONThe expression rate of Bcl-2/Bax in unstable plaques was higher than in stable plaques. Bcl-2 was one of the elements that maintain plaque stability whereas Bax was one element that facilitates plaque instability. Therefore, Bcl-2/Bax expression in different stage of atherosclerosis may be one of the molecule regulation mechanisms in carotid atherosclerosis.

Apoptosis ; genetics ; Carotid Arteries ; metabolism ; pathology ; Carotid Artery Diseases ; metabolism ; Carotid Stenosis ; metabolism ; pathology ; Endothelium, Vascular ; metabolism ; Humans ; Macrophages ; metabolism ; Muscle, Smooth, Vascular ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Up-Regulation ; bcl-2-Associated X Protein

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.
Humans ; Endothelial Cells/metabolism* ; Cardiovascular Diseases ; Medicine, Chinese Traditional ; Atherosclerosis/prevention & control* ; Lipoproteins, LDL/metabolism* ; Endothelium, Vascular ; Plaque, Atherosclerotic ; Autophagy