Animals ; Cardiovascular Diseases ; genetics ; pathology ; Cell Proliferation ; Genes ; Microfilament Proteins ; genetics ; Muscle Proteins ; genetics ; Muscle, Smooth, Vascular ; pathology ; Rats

This article reviews the recent literature of 'vascular depression' hypothesis. The 'vascular depression' hypothesis is supported by the evidence for associations between vascular disease and late-onset depression and between ischemic brain lesions and distinctive depressive symptoms. Patients with vascular depression is characterized by late-onset, absence of family history of mood disorders, evidence of vascular disease or vascular risk factors, cognitive impairment, psychomotor retardation, limited depressive ideation, poor insight, and disability. Vascular depression may be the entity suitable for studies of mechanism of depression. Depression in later life is often under-diagnosed and under-treated. Drugs used in the prevention and treatment of cerebrovascular disease may be shown to be beneficial influences for the prevention of vascular depression. Combined treatment with antidepressant and cognitive-behavioral rehabilitation will be more helpful. In the future, developments in structural and functional imaging, electrophysiology, chronobiology, and genetics will permit the knowledge of the association between mood disorders and brain lesions.
Brain ; Depression* ; Electrophysiology ; Genetics ; Humans ; Mood Disorders ; Psychomotor Disorders ; Rehabilitation ; Risk Factors ; Vascular Diseases

BACKGROUND/AIMS: Vascular access dysfunction is an important cause of morbidity and mortality in hemodialysis (HD) patients. Recent studies have shown that a klotho gene mutation is related to endothelial dysfunction, thrombosis, and arteriosclerosis, which are regarded as causes of vascular access dysfunction. We investigated the relationship between the klotho G-395A polymorphism and early dysfunction in vascular access in HD patients. METHODS: Patients who underwent vascular access operations between 1999 and 2002 were enrolled (n=126). Genotyping was performed by allelic discrimination using a 5'-nuclease polymerase chain reaction assay. Clinical data that could be relevant to access dysfunction were obtained from medical records. Early dysfunction of vascular access was defined as the need for any angioplastic or surgical intervention to correct or replace a poorly or nonfunctioning vascular access within 1 year and at least 8 weeks after initial access placement. RESULTS: Of the 126 patients, the genotype frequency of G-395A was 72.2% for GG (n=91), 24.6% for GA (n=31), and 3.2% for AA (n=4), and the frequency of minor allele was 0.155. Clinical data were similar between the two groups, divided according to the status of the A allele. Early dysfunction occurred in 34 (27.0%) of patients, but it occurred at a significantly higher rate in A allele carriers (45.7%, 16/35) than in noncarriers (19.8%, 18/91; p=0.003). CONCLUSIONS: Our results suggest that the klotho G-395A polymorphism could be a risk factor for early dysfunction of vascular access in HD patients.
Aged ; *Arteriovenous Shunt, Surgical ; Catheters, Indwelling ; Cohort Studies ; Female ; Glucuronidase/*genetics ; Humans ; Kidney Failure, Chronic/complications/*genetics/therapy ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Promoter Regions, Genetic/genetics ; *Renal Dialysis ; Vascular Diseases/complications/genetics ; Vascular Patency/*genetics

Polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T is one of the suggested risk factors for atherosclerosis. However, few studies have reported on the relationship between MTHFR C677T polymorphism and vascular calcification (VC) in chronic hemodialysis patients. We investigated the relationship between the MTHFR C677T polymorphism and VC in 152 chronic hemodialysis patients. Patients with a TT genotype exhibited significantly higher VC scores than patients expressing CC and CT (P = 0.002). The prevalence of peripheral vascular disease increased with the incidence of MTHFR C677T mutations for all patients, and the incidence of cerebrovascular accidents also increased with the presence of mutations for young patients (< or = 60 yr) (P < 0.05). Patients with CT and TT genotypes had adjusted odds ratios for VC of 1.39 and 1.58, respectively (P < 0.05). In summary, these data suggest that the MTHFR C677T polymorphism affects the degree of VC in chronic hemodialysis patients.
Aged ; Calcinosis/*genetics ; Genetic Predisposition to Disease ; Humans ; Kidney Failure, Chronic/*genetics ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; *Renal Dialysis ; Risk Factors ; Vascular Diseases/*genetics

The NLRP3 inflammasome, a protein complex belonging to the family of nucleotide-binding and oligomerization domain like receptors (NLRs), plays a vital role in the innate immune system. It promotes pro-caspase 1 cleavage into active caspase-1, which contributes to maturation and releases of IL-1β and IL-18 in response to the harmful signals and participates in the host immune response and sterile inflammation. Recently a large number of studies have shown that NLRP3 inflammasome closely relates to the pathogenesis of the vascular diseases. NLRP3 inflammasome, which involves in the sterile inflammation of the vascular wall, plays an important role in the pathogenesis of main, middle and small arteries.
Caspase 1 ; immunology ; metabolism ; Gene Expression Regulation ; genetics ; immunology ; Humans ; Inflammasomes ; immunology ; Inflammation ; complications ; genetics ; Interleukin-18 ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; NLR Family, Pyrin Domain-Containing 3 Protein ; immunology ; Signal Transduction ; genetics ; immunology ; Vascular Diseases ; etiology ; genetics ; immunology

Blood stasis syndrome is one of the pathological concepts of Oriental traditional medicine. In Oriental traditional medicine, blood is thought of as not only blood but also as a living component of the body. In fact, blood stasis syndrome is related to not just circulation disorders but dermatological and gynecological and other diseases. In Japan, the concept of blood stasis syndrome is based on the past literature, for instance, Synopsis of Golden Chamber (Jin Kui Yao Lue), etc. There are many signs of this syndrome, such as a dry mouth, fullness of the abdomen and rough skin. However, the levels of importance of these signs had been unclear. Therefore, in order to determine the levels of seriousness, a scoring system of blood stasis syndrome was made based on multivariate analysis by Dr. Terasawa (Terasawa's Blood Stasis Score). Using the scoring system, we have studied blood stasis syndrome mainly related to blood circulation using modern techniques of analysis. From the results, we found that patients with blood stasis syndrome showed hemorheological abnormalities, and an improvement in these abnormalities was shown after administration of removing-blood stasis formulae. Furthermore, we have studied blood stasis syndrome from the point of view of molecular biology. We searched for the specific protein expression in blood stasis syndrome by proteomic analysis, and found no specific protein expression. However, there may be a possibility of developing a diagnostic algorithm for blood stasis by construction of a decision tree. During the past few years, as one of the molecular biological factors affecting blood stasis syndrome, we have been studying hypoxia inducible factor, which is located in the upstream of many genes. Above all, blood stasis syndrome is more than just circulatory deficit but encompasses the pathological concept of constant multilateral change in the living body.
Algorithms ; Coronary Disease ; diagnosis ; genetics ; Diagnosis, Differential ; Hemorheology ; Humans ; Japan ; Medicine, East Asian Traditional ; methods ; Molecular Biology ; methods ; Vascular Diseases ; diagnosis ; genetics

Livedoid vasculopathy is a rare chronic relapsing disorder characterised by recurrent painful thrombotic and vasculitic ulcers on the legs. We present the cases of two Indian women with livedoid vasculopathy that were found to be associated with an underlying factor V Leiden heterozygous mutation. There were no other thrombotic manifestations, and livedoid vasculopathy was the sole presenting feature of the factor V Leiden mutation, although this could also be coincidental. Initial treatment with high-dose immunosuppressive therapy was suboptimal, and the addition of pentoxifylline and antiplatelet therapy was crucial in achieving disease control and remission. These cases highlight the possible association with an underlying prothrombotic disorder, such as factor V Leiden mutation, in patients with livedoid vasculopathy. Although this association is relatively uncommon, it is more relevant to Indian patients, as the presence of factor V Leiden mutation is highest in this ethnicity as compared to the local Malay and Chinese populations.
Adult ; Blood Vessels ; pathology ; DNA ; genetics ; Factor V ; genetics ; metabolism ; Female ; Humans ; Leg Ulcer ; blood ; genetics ; pathology ; Livedo Reticularis ; blood ; diagnosis ; genetics ; Point Mutation ; Polymerase Chain Reaction ; Skin ; blood supply ; Skin Diseases, Vascular ; blood ; genetics ; pathology

This phase 1 clinical trial tested the safety of intramuscular gene transfer by using naked plasmid DNA encoding the gene for VEGF, and analyzed the potential therapeutic benefits in patients with severe peripheral arterial disease (PAD). This study was an open-labeled, dose- escalating, single-center trial on nine male patients with severe debilitating PAD who had not responded to conventional therapy. Seven had Buerger's disease and two had arteriosclerosis obliterans. Plasmid DNA (pCK) containing human VEGF165 was given by eight intramuscular injections in and around the area in need of new blood vessels. The study evaluated three escalating total doses (2, 4, and 8 mg of pCK- VEGF165), with half of each total dose given four weeks apart. The follow-up duration was nine months. The gene injections were well tolerated without significant side effects or laboratory abnormalities related to gene transfer. Three patients showed transient edema in their extremities. Ischemic pain of the affected limb was relieved or improved markedly in six of seven patients. Ischemic ulcers healed or improved in four of six patients. The mean ankle-brachial index (ABI) improved significantly. Six of nine patients showed an increase in collateral vessels around the injection sites demonstrated by digital subtraction angiography. However, there was no relationship between the degree of ABI improvement and the dose given. Mean plasma levels of VEGF did not increase significantly. In conclusion, intramuscular injections of pCK- VEGF165 can be performed safely to induce therapeutic angiogenesis in patients with severe PAD.
Adult ; Aged ; Angiography, Digital Subtraction ; Arterial Occlusive Diseases/*therapy ; Foot/pathology ; *Gene Therapy ; Gene Transfer Techniques ; Humans ; Injections, Intramuscular ; Male ; Middle Aged ; *Neovascularization, Physiologic ; Peripheral Vascular Diseases/*therapy ; Research Support, Non-U.S. Gov't ; Vascular Endothelial Growth Factor A/*genetics

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

Vascular endothelial growth factor, VEGF, is essential for endothelial cell differentiation (vasculogenesis) and for the sprouting of new capillaries from preexisting vessels (angiogenesis). In addition, there is strong evidence that VEGF is a survival factor allowing the cells to survive and proliferate under conditions of extreme stress. Hypoxia is a key regulator of VEGF gene expression. Besides hypoxia, many cytokines, hormones and growth factors can up-regulate VEGF mRNA expression in various cell types. VEGF is present in the glomerulus of both the fetal and adult kidney. The VEGF produced by glomerular epithelial cell may be responsible for maintenance of the fenestrated phenotype of glomerular epithelial cells, thus facilitating the high rate of glomerular ultrafiltration. But there is little known about the role of VEGF in the tubule. VEGF is thought to be involved in many kinds of kidney diseases. Whereas VEGF has a beneficial role in the pathogenesis in some diseases, it does harmful action in others. Because VEGF is known to be associated with the pathogenesis of some diseases, such as diabetic nephropathy, renal tumor and polycystic kidney disease, the study about the role of VEGF is going to be a target for disease control. On the other hand, an attempt at enhancing the role of VEGF has to be made at diseases like several ARF models and experimental glomerulonephritis.
Animals ; Endothelial Growth Factors/genetics/*metabolism ; Gene Expression ; Human ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Kidney Diseases/*metabolism/physiopathology ; Kidney Glomerulus/*metabolism ; Kidney Tubules/*metabolism ; Lymphokines/genetics/*metabolism ; Protein Isoforms/genetics/metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors