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PubMed2004

Proteinase-activated Receptor 2 (PAR2): a challenging new target for treatment of vascular diseases.

Proteinase-activated Receptor 2 (PAR2) is a potential target for the design of drug treatments for vascular diseases. Its unique mechanism of activation by serine proteinases, questions regarding the identities of endogenous agonists and its apparent multiple activities in the vasculature contribute to complex pharmacology. The progress of the pursuit to understand the function of PAR2 relies on the design of short specific peptides as selective agonists for PAR2 in receptor-selective cultured cell expression systems and is limited by the lack of any PAR2 antagonists. Fortunately, the utilization of transgenic PAR2-deficient mice enables the identification of the actions of selective PAR2-derived activating peptides attributed to activation solely of PAR2 in more physiologically complex systems. Of multiple pharmacological responses, PAR2-derived peptide agonists reduce vascular tone, and therefore increase blood flow, via nitric oxide-dependent and -independent paracrine actions of the endothelium upon the underlying vascular smooth muscle cells of blood vessels. PAR2-mediated endothelial-dependent relaxation and hyperpolarization of vascular smooth muscle in select arterial vascular beds via a nitric oxide/cyclooxygenases-independent mechanism suggests a strategy for correction of endothelium-based vascular dysfunction. Vascular tissues respond to progression of vascular diseases such as atherosclerosis or to injury with variable changes of PAR2 expression. With further research and drug development, PAR2 agonists and antagonists may become a basis for a new class of therapeutic agents for treatment of vascular diseases.

Animals↗
PubMed1992

Risk factors for peripheral vascular disease in hypertensive subjects with type 2 diabetes mellitus.

Possible factors predisposing to peripheral vascular disease (PVD) in hypertensive subjects with Type 2 diabetes mellitus were studied. Details of age, sex, duration of diabetes, blood pressure, and smoking habit were recorded in 180 subjects of either White, West Indian Black or Asian ethnic origin. Glycosylated haemoglobin, fasting serum total cholesterol, total high density lipoprotein (HDL), HDL2, low density lipoprotein (LDL-cholesterol), and triglycerides were measured in all subjects. Peripheral vascular disease was defined as an ankle/brachial systolic pressure < 1.0 as measured by the Doppler technique. Multivariate analysis was performed and the following factors were identified as being strongly associated with the presence of PVD with a statistical significance of p < 0.001; LDL-cholesterol, total HDL-cholesterol, age, male sex, diet or oral hypoglycaemic therapy, diastolic blood pressure, and of p < 0.003; systolic blood pressure. When blood pressure was excluded from the analysis the other factors retained their predictive value. We conclude that hypertension and dyslipidaemia are important risk factors for peripheral vascular disease in Type 2 diabetes mellitus.

Blood Pressure↗
PubMed2002

Homocysteine, vitamin B6, and vascular disease in AD patients.

BACKGROUND: Cerebrovascular disease is a cause of dementia and is associated with elevated plasma levels of homocysteine. Patients with AD tend to have unexplained elevations of homocysteine concentrations vs healthy control subjects. Vitamin B(6) status, a potential determinant of plasma homocysteine, has not been characterized in patients with AD. OBJECTIVE: To investigate plasma homocysteine, vitamin B(6) status, and the occurrence of vascular disease in patients with AD. METHODS: Forty-three patients with AD and 37 control subjects without AD were studied for homocysteine, B vitamin status (folate, vitamin B(12), pyridoxal-5'-phosphate [PLP]), kidney function (creatinine), and thyroid function (thyroid-stimulating hormone, thyroxin). In addition, the presence of vascular disease was assessed by reviewing both medical histories and brain imaging data provided by CT and MRI. RESULTS: The OR for elevated plasma homocysteine (>12 micromol/L) was only 2.2 (not significant) for subjects with AD. In contrast, the OR was 10.0 (p = 0.03) for subjects with vascular disease (n = 26). The OR for low plasma PLP (<25 nmol/L) was 12.3 (p = 0.01) for patients with AD. No significant relationship was observed between vascular disease and PLP level or between plasma homocysteine and PLP concentrations. CONCLUSIONS: Elevated plasma homocysteine in patients with AD appears related to vascular disease and not AD pathology. In addition, low vitamin B(6) status is prevalent in patients with AD. It remains to be determined if elevated plasma homocysteine or low vitamin B(6) status directly influences AD pathogenesis or progression.

Aged↗
PubMed2006

The prevalence of thrombophilia in patients with symptomatic peripheral vascular disease.

BACKGROUND: The aim of this prospective study was to establish the prevalence of thrombophilia and hyperhomocysteinaemia using a comprehensive screen in patients with peripheral vascular disease. METHODS: A total of 150 patients with peripheral vascular disease (with an ankle brachial pressure index of less than 0.8) underwent thrombophilia screening (protein C and protein S, antithrombin, lupus anticoagulant, activated protein C resistance and factor V Leiden and prothrombin mutations). Fasting homocysteine assays were also performed. RESULTS: A thrombophilia defect was found in 41 patients (27.3 per cent). The commonest was protein S deficiency, found in 17 patients (11.3 per cent). Others included factor V Leiden mutation, found in 10 (6.7 per cent) and protein C deficiency, found in six (4.0 per cent). Lupus anticoagulant and prothrombin mutation were both found in six (4.0 per cent). One patient had an antithrombin deficiency. Only the presence of critical ischaemia was associated with a positive thrombophilia screen on single variable analysis (P = 0.03). Hyperhomocysteinaemia was present in over a third of the study group (37.3 per cent): 45 defined as moderate and 11 as intermediate. CONCLUSION: A quarter of patients with peripheral vascular disease had evidence of thrombophilia, and a third had hyperhomocysteinaemia.

Aged↗
PubMed1999

Progressive pulmonary vascular disease after pulmonary artery banding and total correction in a case of ventricular septal defect and pulmonary hypertension.

A 7-month-old infant with ventricular septal defect and pulmonary hypertension underwent pulmonary artery banding, which resulted in a decrease in the pulmonary arterial peak pressure from 102 to 54 mmHg. Lung biopsy findings showed at most an early grade 3 Heath-Edwards classification, and an index of pulmonary vascular disease of 1.4, both of which indicated operability for total correction. Small pulmonary arteries less than 100 microns in diameter, however, showed marked hydropic changes in the medial smooth muscle cells. Total correction was performed at the age of 2 years, but the pulmonary arterial pressure failed to decrease. A lung biopsy taken just after the closure of the ventricular septal defect contraindicated operability due to progressive pulmonary vascular disease at a grade 6 Heath-Edwards classification and an index of pulmonary vascular disease of 2.4. The patient died at 8 months after the operation, and an autopsy revealed still more advanced pulmonary vascular disease at a grade 6 Heath-Edwards classification and an index of pulmonary vascular disease of 2.8. The pathogenesis of arterial changes is discussed.

Disease Progression↗
PubMed1988

Mucociliary clearance in pulmonary vascular disease.

The mucociliary clearance function was studied by radioaerosol inhalation lung cinescintigraphy and its quantification in 8 patients with pulmonary vascular diseases; pulmonary embolism, 5 cases, and right pulmonary artery hypoplasia, pulmonary arteriovenous fistulas, aortitis syndrome, 1 case each. The mucociliary clearance function was found to be well maintained in pulmonary vascular diseases unless ventilation was disturbed. There was no difference in the mucociliary clearance function between pulmonary embolism and other pulmonary vascular diseases.

Adolescent↗
PubMed2002

Pulmonary hypertension in collagen vascular disease.

Pulmonary hypertension is a serious but often overlooked complication in collagen vascular disease. The understanding of the development of pulmonary hypertension has increased substantially during the last years. Abnormal proliferation of pulmonary vascular cells is now being regarded as a predominant process leading to pulmonary vascular obliteration. Medical therapy focuses on prostacyclin treatment, which has been shown to improve exercise capacity and haemodynamic variables in patients with several collagen vascular diseases and pulmonary arterial hypertension. Continuous intravenous prostacyclin remains the standard treatment of associated pulmonary hypertension but less invasive alternatives such as subcutaneous treprostinil, oral beraprost or aerosolized iloprost, as well as, novel substances such as endothelin receptor antagonists may be appropriate for selected patients.

Collagen Diseases↗
PubMed1983

Pulmonary vascular disease in secundum atrial septal defect in childhood.

Pulmonary vascular structure was analyzed in the lungs of 10 patients with a secundum atrial septal defect (ASD) in whom pulmonary hypertension had developed. Four patients were aged 6 months or less, 5 were aged 2 to 9 years, and 1 was 21 years old. Pulmonary vascular structure was analyzed using lung biopsy tissue in 5 and autopsy material in the other 5. All the infants presented with heart failure and all had a marked increase in pulmonary arterial smooth muscle; only 1 infant survived surgery. Of the 5 older children, 1 presented with cyanosis, but in the rest the ASD was incidental to the presentation. Three patients had severe pulmonary vascular disease, similar to that seen in adults with a hypertensive ASD. Only 2 older children underwent successful surgery. In 1 child and in the 1 adult, the severity of the pulmonary vascular disease precluded surgery. The ASD was closed in 8 patients, but only 3 survived. Pulmonary hypertension develops rarely in secundum ASD in childhood.

Adolescent↗
PubMed1988

Percutaneous laser angioplasty in the treatment of peripheral vascular disease.

For a long time the treatment of peripheral vascular diseases mainly was a surgical one. Improvements in drug therapy and success of PTCA have increased the interest in a more conservative therapy. So laser promised to be another tool in the percutaneous treatment of peripheral vascular diseases. First successful experiments were followed by the experience of technical problems and side effects of this new method. First clinical studies in occluded human femoral arteries were started at Stanford University in 1983. The results, published in 1985, showed that occlusive lesions in this vascular region could be successfully reopened by a percutaneous approach. But in cases of severe calcification the danger of perforation or dissection was significantly increased. Moreover the newly created channel proved to be too small for a sufficient revascularization, so that this method had to be combined with balloon angioplasty. By the development of the metalcapped "hot tip", laser energy was totally changed into thermal energy. By this new system greater channels of 2 up to 2.5 mm could be created and by the special design of the metalcap thermal injury to the arterial wall could be decreased. Nevertheless perforation occurred also with this system. Moreover, additional balloon angioplasty was still necessary in proximal segments of the femoral artery. Futural developments of greater metal heads may lead to the exclusive use of the "hot tip" especially in more distal parts. Longterm results will show, if laser angioplasty is comparable to other conventional methods like balloon angioplasty or surgery. There is still a long way to go, until the ideal of reopening atherosclerotic stenoses only by laser energy can be reached.

Angioplasty, Balloon↗
PubMed1989

Peripheral vascular disease. Rheologic variables during controlled ischemia.

The quantitative and qualitative behavior of hemorheologic factors both at rest and after treadmill exercise in 30 male patients with stage II peripheral vascular disease compared with 20 sex- and age-matched healthy controls have been studied. The aim of our study was to identify functional rheologic markers for peripheral vascular disease. At rest, whole blood viscosity (corrected for hematocrit at both high and low shear rates), fibrinogen levels (4.23 +/- 1.39 vs. 3.23 +/- 1.5), and white blood cell count (7.05 +/- 1.25 vs. 6.03 +/- 1.28) were significantly different between patients and controls. After treadmill exercise, white blood cell counts increased in both patients and controls, whereas only the filterability of mononuclear leukocytes showed a significant variation in the patient group (5.47 +/- 1.54 vs. 7.26 +/- 2.00, p less than 0.002). In this group, mononuclear filterability improved during the recovery period. The results suggest a relation between exercise-induced ischemia of the lower limb and mononuclear filterability in patients with peripheral vascular disease. Mononuclear filterability could be a functional rheologic marker for peripheral vascular disease.

Blood Component Removal↗
PubMed1996

Self-reported smoking in vascular disease: the need for biochemical confirmation.

The relationship between smoking and vascular disease requires reliable information on the smoking status of patients suffering these disorders. As self-reported smoking status is unreliable and therefore misleading, biochemical markers (such as serum thiocyanate) provide a more accurate guide to smoking status. This study compared the self-reported and biochemical marker data (serum thiocyanate) for two different groups: 215 patients with peripheral vascular disease (PVD) and 124 with ischaemic heart disease (IHD). The object of the comparison was to assess if there was any difference between the two groups with regard to denial of smoking. The PVD group had more smokers by either criterion (verbal 34% in PVD, 15% in IHD, P < 0.001: thiocyanate level > 12.5 micrograms ml-1, 47% in PVD, 34% in IHD, P < 0.05). Of those verbally claiming and biochemically assessed as smokers, 55% of those with IHD and 28% of those with PVD denied using cigarettes. Our data point to differences in verbal reporting of smoking between patients with IHD and PVD. This probably reflects the patient's perception of the dangers of smoking and their diseases and may have clinical consequences for the collection of accurate data on the influence of this risk factor on atherosclerosis.

Biomarkers↗
PubMed2002

The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin.

BACKGROUND: Bilirubin and albumin may act as antioxidants. Their circulating levels are lower in those patients with ischemic heart disease (IHD) and could be further reduced by more extensive atherosclerosis, i.e. peripheral vascular disease (PVD). METHODS: Serum bilirubin and albumin were measured in 456 patients classified into 3 groups: 1) no clinically evident cardiovascular disease (CVD), 2) IHD present and 3) PVD present. Smoking status and gender (which affect bilirubin and albumin levels in healthy individuals) were considered separately. RESULTS: Bilirubin was lower in smoking men without CVD or with PVD than in non-smokers (p=0.02 and p=0.04, respectively) in the same groups. Non-smoking women without CVD had significantly (p=0.004) lower bilirubin levels than the corresponding group of men. Frequency analysis of male non-smokers revealed significantly (p=0.04) more patients with a lower bilirubin (<6.5 mmol/l) in the PVD compared with the no CVD group. Albumin levels showed the same trends. CONCLUSIONS: Prospective studies should consider smoking and gender when assessing the relevance of bilirubin and/or albumin levels in patients with vascular disease. Our findings support those of other studies that show that low serum bilirubin and albumin levels are associated with the presence of vascular disease.

Age Factors↗
PubMed1977

Pulmonary vascular disease complicating the Blalock-Taussig anastomosis.

The pulmonary vascular bed was evaluated following a Blalock-Taussig shunt performed in 36 patients for decreased pulmonary blood flow. The time of follow-up ranged from one to 21 years after operation. No patients developed severe pulmonary changes in less than eight years after institution of the shunt. Ten of 20 patients having a shunt eight years or longer developed some degree of pulmonary vascular disease, mainly in the form of intimal fibrosis. This was severe in six of the 20 patients. As the duration of the shunt increased, so did the incidence of pulmonary vascular disease.

Adolescent↗
PubMed1991

Collagen vascular diseases of childhood.

This article is devoted to collagen vascular diseases of childhood. The connective tissue diseases that are discussed are lupus erythematosus, scleroderma, and dermatomyositis. Of the vasculitic syndromes, Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, and polyarteritis nodosa are discussed. Although the collagen vascular diseases are rare in the pediatric age group, when they occur they can be very serious.

Adolescent↗
PubMed1992

Lipoprotein [Lp(a)] and peripheral vascular disease.

Lipoprotein(a) [Lp(a)], which combines structural elements of the lipid and fibrinolytic systems, is a major independent risk factor for the development of coronary heart disease. Eighty-four consecutive patients with peripheral vascular disease (of whom 42 had concomitant ischaemic heart disease) and 43 healthy controls were enrolled in a case-control study. We found that the mean Lp(a) concentration in male patients with peripheral vascular disease (PVD) was almost threefold higher than that of controls, while in female patients the Lp(a) concentration was more than twice that of controls. This marked difference was borne out in patients with and without concomitant ischaemic heart disease (IHD). A multivariate logistic regression analysis indicated that Lp(a) is independently associated with PVD when adjusted for age and sex (odds ratio per 100 mg l-1 increase in Lp(a) = 1.35; P < 0.01). A similar association is observed for patients with concomitant IHD (odds ratio per 100 mg l-1 increase in Lp(a) = 1.65; P < 0.01).

Aged↗
PubMed2006

A simple noninvasive test to detect vascular disease in patients with erectile dysfunction: a novel method.

INTRODUCTION: The association between erectile dysfunction (ED) and cardiovascular disease (CVD) is becoming increasingly evident. Both conditions are thought to share a common denominator, which is endothelial dysfunction. Therefore, testing endothelial function in ED patients may serve to detect vascular disease in this cohort of patients. AIMS: To investigate whether measuring the reactive hyperemic response (RHR) of the forearm vessels through a simple noninvasive method could identify vascular disease in patients with ED. PATIENTS AND METHODS: Forty-eight male subjects were recruited into the study, 35 of whom presented to the sexual dysfunction clinic with a complaint of ED, and 13 healthy subjects served as a control group. The ED patients were subdivided into two groups, according to the presence or absence of CVD or its risk factors. The RHR of the forearm vessels was measured noninvasively in all subjects by using a handheld Doppler device. RESULTS: Significant reduction in the peak systolic velocity ration was observed in ED patients with concomitant CVD or risk factors in comparison with the other ED patients with no CVD or risk factors and the control group. Results were highly significant on both occasions (P < 0.001). The 50% recovery time was not significantly different between any of the groups (P > 0.05). CONCLUSION: Our results suggest that those patients with impaired RHR have an abnormality in their vascular system, which is likely to be the cause of their ED and CVD. Using this simple noninvasive method can help to identify vascular disease in ED patients. It can also be used to suggest vascular disease in any patient, where further tests might be indicated.

Adult↗
PubMed1977

Factors in the rehabilitation of patients with peripheral vascular disease.

At some point in the progression of peripheral vascular disease, a hospitalized patient may require the services of a rehabilitation unit. All patients, however, can benefit from basic rehabilitative care that should begin at the time of initial diagnosis of their disease and be considered throughout their treatment course. The nurse in the clinic , in the intensive care unit, and on the medical and surgical units should be aware of potential factors that may prevent the person with peripheral vascular disease from realizing his full potential. Physical, psychologic, social, economic, vocational, and spiritual needs are all important factors in the rehabilitation process.

Activities of Daily Living↗
PubMed1978

Hormonal profile, blood sugar control and HLA patterns in long-term insulin dependent diabetes with and without vascular disease.

Nineteen insulin dependent diabetics with onset at 30 years of age or less and duration of diabetes of greater than 25 years were divided into two groups on the basis of the presence or absence of clinically evident vascular disease. The patients without vascular disease were characterised by a later mean age of onset, lower fasting growth hormone concentration, and a lower frequency of the unusual HLA pattern B8 without A1 compared to the diabetics with vascular complications. The level of blood glucose control assessed over the last 15 years, insulin antibody titres, plasma glucagon levels and plasma cholesterol did not differ between the two groups. Residual beta cell activity was found in only one of the 19 patients. Although this study does not exclude an effect of the degree of blood glucose control or persistence of beta cell function in the early stages of diabetes on the subsequent development of vascular disease, it suggests that genetic factors, age of onset and plasma growth hormone levels may be more important.

Adult↗