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PubMed2000

Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women.

BACKGROUND: The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the L-arginine-nitric oxide (NO) pathway and oxidative stress. Methods and Results-In 26 healthy women (age, 45.7+/-5.4 years) and 18 fertile women with leiomyoma (age, 44.5+/-5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0. 15, 0.45, 1.5, 4.5, or 15 microgram. 100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, or 4 microgram. 100 mL(-1). min(-1)), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during L-arginine (200 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or N(G)-monomethyl-L-arginine (L-NMMA; 100 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or vitamin C (8 mg. 100 mL(-1). min(-1); 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 beta-estradiol TTS, 50 microgram/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by L-arginine and L-NMMA, respectively (P<0.05), but was unaffected by indomethacin or vitamin C. After ovariectomy, the modulating effect of L-arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine (P<0.05). ERT restored L-arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT. CONCLUSIONS: Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.

Acetylcholine↗
PubMed2002

Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in Type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction.

Uncomplicated Type 1 (insulin-dependent) diabetes mellitus is characterized by generalized vasodilatation. Its possible correlates, increased microvascular permeability and endothelial dysfunction, have been associated with long-term complications. The objective was to study the effects of acute hyperglycemia and hyperinsulinemia, both separately and in combination, on skin microvascular flow, capillary permeability, capillary recruitment, and endothelial dysfunction in Type 1 diabetes mellitus. Sixteen Type 1 diabetic patients (all normoalbuminuric, no (pre-)proliferative retinopathy) underwent a euglycemic (glucose target 5.0 mmol/L, insulin infused at 30 mU x kg(-1) x h(-1)), a hyperglycemic (glucose target 12.0 mmol/L, insulin 30 mU x kg(-1) x h(-1)), a hyperinsulinemic (glucose target 5.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)), and a hyperglycemic-hyperinsulinemic (glucose target 12.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)) clamp on separate days, in random order. Skin microvascular flow was measured by laser Doppler flowmetry. Capillary permeability and density were determined by large-window sodium-fluorescein videodensitometry. Increases in serum soluble intercellular adhesion molecule-1 (sICAM-1) and plasma von Willebrand factor antigen (vWF-Ag) were considered to represent abnormal endothelial function. Hyperglycemia (P < 0.01) and hyperinsulinemia (P < 0.05) as well as both interventions combined (P < 0.001) induced an increase in laser Doppler flow, without capillary recruitment. Transcapillary leakage of sodium-fluorescein and sICAM-1 and vWF-Ag levels were unaffected by hyperglycemia or hyperinsulinemia. Microvascular permeability appears to be determined primarily by properties of the capillary wall and not by acute changes in local hemodynamics. The acute hyperglycemia- and hyperinsulinemia-induced vasodilatation is not accompanied by changes in microvascular permeability or endothelial markers.

Acute Disease↗
PubMed2000

Vascular bed heterogeneity in age-related endothelial dysfunction with respect to NO and eicosanoids.

1. Endothelial dysfunction has been described with ageing but the mechanisms responsible have not been clearly elucidated and might be different from one vessel to the other. This study assesses the relative contribution of endothelial nitric oxide (NO) and cyclo-oxygenase (COX) metabolites in relaxation to acetylcholine with ageing in the aorta and the small mesenteric artery of the rat. 2. In the aorta and branch II or III of superior mesenteric artery (SMA), endothelium-dependent relaxation to acetylcholine was not different between 12 - 14 (adult) and 32-week-old rats whereas it was reduced at 70 - 100 (old) weeks of age. 3. Despite an increased endothelial NO-synthase protein expression, the NO-synthase inhibitor, N(G)-nitro-L-arginine-sensitive component of relaxation decreased with ageing. 4. In old rats, exposure to the COX inhibitor, indomethacin, but not the selective COX-2 inhibitor, NS-398, potentiated response to acetylcholine. The thromboxane A(2)/prostaglandin H(2) receptor antagonist, GR 32191B enhanced relaxation to acetylcholine in aorta but it had no effect in SMA. Furthermore, acetylcholine increased thromboxane B(2) production (enzymeimmunoassay) in aorta but not in SMA. Finally, Western blot analysis showed enhanced expression of COX-1 and 2 in the two arteries with ageing. 5. These results suggest that the decrease in acetylcholine-induced relaxation with ageing involves reduced NO-mediated dilatation and increased generation of vasoconstrictor prostanoids most likely from COX-1. They also point out vascular bed heterogeneity related to the nature of prostanoids involved between the aorta (i.e., thromboxane A(2)) and the SMA (unidentified) arteries even though increased expression of COX occurs in both vessels.

Acetylcholine↗
PubMed2001

Coronary endothelial dysfunction after ischemia and reperfusion: a new therapeutic target?

Although cardiac ischemia is usually characterized as a disease of the myocyte, it is clear that the vasculature, and especially endothelial cells, is also a major target of this pathology. Indeed, using a rat model of ischemia/reperfusion, we were able to detect severe endothelial dysfunction (assessed as a decreased response to acetylcholine) after acute or chronic reperfusion. Given the essential role of the endothelium in the regulation of vascular tone, as well as platelet and leukocyte function, such a severe dysfunction could lead to an increased risk of vasospasm, thrombosis and accelerated atherosclerosis. This dysfunction can be prevented by free radical scavengers and by exogenous nitric oxide. Endothelial dysfunction can also be prevented by preconditioning with brief periods of intermittent ischemia, thus extending to coronary endothelial cells the concept of endogenous protection previously described at the myocyte level. Experiments performed on cultured cells showed that the endothelial protection induced by free radical scavengers or by preconditioning was due to a lesser expression of endothelial adhesion molecules such as intercellular adhesion molecule-1, leading to a lesser adhesion of neutrophils to endothelial cells. Identification of the mechanisms of this protection may lead to the development of new strategies aimed at protecting the vasculature in ischemic heart diseases.

Acetylcholine↗
PubMed1991

Endothelial dysfunction in myocardial ischemia and reperfusion: role of oxygen-derived free radicals.

Myocardial ischemia followed by reperfusion results in endothelial dysfunction in cats. This dysfunction is characterized by a loss of endothelium-derived relaxing factor (EDRF) release in response to endothelium-dependent dilators. This loss of endothelium-dependent relaxation (EDR) occurs significantly at 2.5 min post-reperfusion and the dysfunction progresses until it is complete at 20 min post-reperfusion. This reduced EDR is prevented by superoxide dismutase, but not by hydroxyl radical scavengers. In contrast, neutrophil accumulation in the heart, as measured by cardiac myeloperoxidase (MPO) activity, does not reach significant levels until 3 h post-reperfusion, and significant myocardial necrosis does not occur until 4.5 h post-reperfusion. No significant changes in EDR, MPO or cardiac necrosis occurred during the 90 min of ischemia. Thus, endothelial dysfunction is an early and specific marker of reperfusion injury preceding neutrophil involvement and cardiac necrosis. Superoxide radicals appear to play a key role in the decreased EDR observed early after reperfusion.

Animals↗
PubMed2000

Endothelial dysfunction in arterial hypertension.

Systemic arterial pressure is a dynamic and reactive physiological parameter depending on a great many factors. The endothelial cells of the vascular system are responsible for many biochemical reactions maintaining vascular homeostasis and therefore arterial pressure. Arterial hypertension, atherosclerosis and endothelial dysfunction constitute risk factors increasing morbidity and mortality of cardiovascular origin. These three elements are closely related and frequently act simultaneously damaging different organs. In this paper we review the physiology of the endothelium and the probable consequences of endothelial dysfunction on the pathophysiology of arterial pressure.

Arteries↗
PubMed2001

[Molecular mechanisms of endothelial dysfunction in diabetes mellitus].

Diabetes is a strong risk factor for vascular diseases. Recent studies have shown that disruption of endothelial cell function results in vascular injury. One of causes underlying the endothelial dysfunction in diabetics is hyperglycemia. Many epidemiological studies demonstrated that hyperglycemia increased the incidence of macrovascular diseases. In contrast to the microvascular complications in diabetes, however, the macrovascular complication often develops even in patients with good glycemic control, suggesting that some factors other than hyperglycemia may contribute to it. Insulin resistance is one of possible candidates for that. In fact, it is shown that insulin resistance is an independent risk factor for atherosclerosis. In this article, we reviewed recent hypothesis explaining how hyperglycemia or insulin resistant state caused endothelial dysfunction.

Animals↗
PubMed1998

Aspirin improves endothelial dysfunction in atherosclerosis.

BACKGROUND: The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. We hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action can be reversed by aspirin. METHODS AND RESULTS: In 14 patients with coronary atherosclerosis and 5 with risk factors, we tested femoral vascular endothelial function with acetylcholine and substance P and endothelium-independent function with sodium nitroprusside before and after intravenous aspirin. Drugs were infused into the femoral artery, and Doppler flow velocity was measured. Acetylcholine-induced but not substance P-or sodium nitroprusside-induced vasodilation was lower in patients with atherosclerosis than in those with only risk factors. Aspirin had no baseline effect but improved acetylcholine-mediated vasodilation only in patients with atherosclerosis; at the peak dose, acetylcholine-mediated femoral vascular resistance index was 19 +/- 5%, P=.002 lower. There was a correlation between the baseline response to acetylcholine and the magnitude of improvement with aspirin (r=.5, P=.05). Thus, patients with a depressed response to acetylcholine had greater improvement with aspirin, and vice versa. The presence of atherosclerosis was an independent determinant of improvement with aspirin. Aspirin had no effect on the responses to either substance P or sodium nitroprusside. CONCLUSIONS: Cyclooxygenase-dependent, endothelium-derived vasoconstrictor release modulates acetylcholine-induced peripheral vasodilation in patients with atherosclerosis. Improvement of endothelial dysfunction with aspirin may improve vasodilation, reduce thrombosis, and inhibit progression of atherosclerosis and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis.

Acetylcholine↗
PubMed2000

Comparison of zofenopril and lisinopril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure.

We evaluated the role of SH-groups in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. To this end, we compared the vasoprotective effect of chronic treatment with zofenopril (plus SH-group) versus lisinopril (no SH-group), or N-acetylcysteine (only SH-group) in myocardial infarcted (MI) heart failure rats. After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium-dependent and -independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS-inhibitor L-NMMA to determine NO-contribution. Total dilatation after receptor-dependent stimulation with acetylcholine (ACh) was attenuated (-49%, P<0.05) in untreated MI (n=11), compared to control rats with no-MI (n=8). This was in part due to impaired NO-contribution in MI (-50%, P<0.05 versus no-MI). At the same time the capacity for generation of biologically active NO after receptor-independent stimulation with A23187 remained intact. Chronic treatment with n-acetylcysteine (n=8) selectively restored NO-contribution in total dilatation to ACh. In contrast, both ACE-inhibitors fully normalized total dilatation to ACh, including the part mediated by NO (no significant differences between zofenopril (n=10) and lisinopril (n=8)). Zofenopril, but not lisinopril, additionally potentiated the effect of endogenous NO after A23187-induced release from the endothelium (+100%) as well as that of exogenous NO provided by nitroglycerin (+22%) and sodium nitrite (+36%) (for all P<0.05 versus no-MI). We conclude that ACE-inhibition with a SH-group has a potential advantage in improvement of endothelial dysfunction through increased activity of NO after release from the endothelium into the vessel wall. Furthermore, this is the first study demonstrating the selective normalizing effect of N-actylcysteine on NO-contribution to ACh-induced dilatation in experimental heart failure.

Acetylcholine↗
PubMed2003

Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis.

Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction or with diffuse white matter changes, with the imaging appearance of leukoaraiosis. Endothelial dysfunction, which can lead to breakdown of the blood-brain barrier, impaired cerebral autoregulation and prothrombotic changes, is believed to be important in mediating disease. Circulating levels of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are markers of endothelial activation and damage, and may provide insights into disease pathogenesis or differences between phenotypes. We therefore measured these markers in a prospective series of patients with lacunar stroke. One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied. Markers of endothelial function were measured on venous blood samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (n = 47) and ischaemic leukoaraiosis, defined as a clinical lacunar stroke and leukoaraiosis on brain imaging (n = 63). The number of lacunes and severity of leukoaraiosis were also scored on MRI. ICAM1, TM and TFPI were elevated in cerebral SVD subjects compared with controls (P <or= 0.006). The ischaemic leukoaraiosis group had a different endothelial marker profile, with lower levels of TFPI (P = 0.01) and a higher TF/TFPI ratio (P = 0.01) compared with the isolated lacunar infarction group. TM levels were associated with the number of lacunes (P = 0.008) and the leukoaraiosis score (P = 0.03), but TF levels and the TF/TFPI ratio were associated only with the extent of leukoaraiosis (P <or= 0.02). These results suggest that there is evidence of chronic endothelial dysfunction in cerebral SVD, and endothelial prothrombotic changes may be important in mediating the ischaemic leukoaraiosis phenotype. Therapies which help to stabilize the endothelium may have a role in this group of patients.

Aged↗
PubMed2001

Association of maternal endothelial dysfunction with preeclampsia.

CONTEXT: Preeclampsia is believed to result from release of placental factors that damage maternal vascular endothelium. However, because most studies have been conducted during pregnancy, it has not been possible to separate maternal from placental mechanisms underlying endothelial dysfunction in preeclampsia. OBJECTIVE: To determine whether endothelial function is impaired in nonpregnant women with previous preeclampsia and whether endothelial dysfunction is mediated by oxidative stress. DESIGN AND SETTING: Case-control study conducted at 3 hospital maternity units in London, England, between July 1997 and June 2000. PARTICIPANTS: A total of 113 women with previous preeclampsia (n = 35 with recurrent episodes; n = 78 with a single episode) and 48 women with previous uncomplicated pregnancies, all of whom were at least 3 months (median, 3 years) postpartum. MAIN OUTCOME MEASURES: Brachial artery flow-mediated (endothelium-dependent) and glyceryl trinitrate-induced (endothelium-independent) dilatation were compared between previously preeclamptic women and controls. To investigate oxidative stress, these measurements were repeated after administration of ascorbic acid, 1 g intravenously, in 15 cases and 15 controls. RESULTS: Mean (SD) flow-mediated dilatation was lower in women with previous preeclampsia compared with controls (recurrent group, 0.9% [4.1%]; single-episode group, 2.7% [3.5%]; and control group, 4.7% [4.3%]; P<.001). In contrast, glyceryl trinitrate-induced dilatation was similar in the 3 groups (recurrent, 19.5% [5.9%]; single-episode, 21.0% [8.0%]; and control, 21.0% [8.3%]; P =.65). Impaired flow-mediated dilatation in previously preeclamptic women was not accounted for by recognized vascular risk factors. Ascorbic acid administration increased flow-mediated dilatation in previously preeclamptic women (baseline, 2.6% [3.3%]; after administration, 5.6% [3.0%]; P =.001) but not in controls (baseline, 6.2% [3.3%]; after administration, 6.7% [5.0%]; P =.72). CONCLUSIONS: Our results indicate that endothelial function is impaired in women with previous preeclampsia and is not explained by established maternal risk factors but is reversed by antioxidant ascorbic acid administration.

Adult↗
PubMed2003

Detection of endothelial dysfunction with brachial artery ultrasound scanning.

The role of the endothelium in human disease recently has become the focus of intense scientific investigation. Impaired endothelial function is associated with a number of disease states, including cardiovascular disease (CVD) and its major risk factors. Endothelial dysfunction precedes overt vascular disease by years and may itself be a potentially modifiable CVD risk factor. Although no gold standard for the measurement of endothelial function exists, the measurement of flow-mediated dilation (FMD) in the brachial artery, assessed with Doppler ultrasonography, is the most studied method and shows the most promise for clinical application. It is a well-tolerated, noninvasive, and low-risk procedure. Brachial artery FMD after transient vascular occlusion may serve as an index of nitric oxide bioavailability, and its impairment correlates with coronary arterial abnormalities. These factors, with the wide availability of vascular ultrasound scanning in clinical practice, make brachial artery FMD an attractive screening tool for endothelial dysfunction. Present limitations of this procedure include the lack of a consensus definition of normal FMD and the variability among centers in both procedural technique and image analysis. However, these limitations are likely to be overcome with increasing experience and advances in technology, and with further refinements, the measurement of brachial artery FMD will likely become the clinical technique of choice for the evaluation of endothelial disease.

Blood Flow Velocity↗
PubMed1995

Plasma endothelin and early coronary endothelial dysfunction in recipients of a cardiac transplant.

Serotonin constricts coronary arteries with endothelial dysfunction, possibly through reduced endothelial release of nitric oxide or enhanced production of constricting factors such as endothelin. Because the plasma levels of this peptide are increased in the early months after cardiac transplantation, we assessed whether a coronary hypersensitivity to the vasoconstrictor effect of serotonin is associated with high plasma endothelin levels. One to 3 months after cardiac transplantation, serotonin (1, 10, or 20 micrograms/min for 2.5 min each) was infused into the coronary circulation in 32 patients. Changes in coronary diameters were determined by quantitative angiography. A > or = 40% reduction in coronary diameter for a dose of serotonin < or = 10 micrograms/min was observed in group A (n = 14) whereas in group B (n = 18), this diameter reduction was never reached even for a 20 micrograms/min infusion of serotonin. Plasma endothelin levels were significantly higher (p < 0.01) in the coronary ostium and coronary sinus in group A, at 23.4 +/- 1.3 pg/ml and 24.9 +/- 0.9 pg/ml versus 12.6 +/- 0.9 pg/ml and 13.8 +/- 1.1 pg/ml, respectively, in group B. These endothelin levels did not significantly change after intracoronary infusion of serotonin. A significant correlation was found between plasma endothelin levels in the coronary ostium and peak coronary constriction (percentage diameter reduction) in both groups (r = 0.77 for group A and r = 0.92 for group B). Thus, early after cardiac transplantation, serotonin-induced coronary constriction is a common finding, and the severity of this abnormality seems to be influenced by plasma endothelin levels.

Blood Pressure↗
PubMed2000

Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia.

Homocysteine is a risk factor for the development of atherosclerosis and its thrombotic complications. We have employed an animal model to explore the hypothesis that an increase in reactive oxygen species and a subsequent loss of nitric oxide bioactivity contribute to endothelial dysfunction in mild hyperhomocysteinemia. We examined endothelial function and in vivo oxidant burden in mice heterozygous for a deletion in the cystathionine beta-synthase (CBS) gene, by studying isolated, precontracted aortic rings and mesenteric arterioles in situ. CBS(-/+) mice demonstrated impaired acetylcholine-induced aortic relaxation and a paradoxical vasoconstriction of mesenteric microvessels in response to superfusion of methacholine and bradykinin. Cyclic GMP accumulation following acetylcholine treatment was also impaired in isolated aortic segments from CBS(-/+) mice, but aortic relaxation and mesenteric arteriolar dilation in response to sodium nitroprusside were similar to wild-type. Plasma levels of 8-epi-PGF(2alpha) (8-IP) were somewhat increased in CBS(-/+) mice, but liver levels of 8-IP and phospholipid hydroperoxides, another marker of oxidative stress, were normal. Aortic tissue from CBS(-/+) mice also demonstrated greater superoxide production and greater immunostaining for 3-nitrotyrosine, particularly on the endothelial surface. Importantly, endothelial dysfunction appears early in CBS(-/+) mice in the absence of structural arterial abnormalities. Hence, mild hyperhomocysteinemia due to reduced CBS expression impairs endothelium-dependent vasodilation, likely due to impaired nitric oxide bioactivity, and increased oxidative stress apparently contributes to inactivating nitric oxide in chronic, mild hyperhomocysteinemia.

Acetylcholine↗
PubMed1995

Clinical relevance of endothelial dysfunction in cardiovascular disorders.

The potential role of endothelial dysfunction, defined by an imbalance in the production of endothelium-derived vasodilator and constrictor factors is discussed. Evidence is presented that increased endothelin-1 production plays an important role in the clinical and morphological manifestations of pulmonary hypertension, particularly in primary disease. As well, the potential contribution of a relative decrease in nitric oxide production to inappropriately elevated pulmonary vascular resistance in patients with secondary causes of pulmonary hypertension, particularly those with congestive heart failure is discussed.

Cardiovascular Diseases↗
PubMed2001

Alteration of plasmalemmal caveolae mimics endothelial dysfunction observed in atheromatous rabbit aorta.

OBJECTIVE: In endothelial cells, nitric oxide (NO) is produced by the endothelial isoform of nitric oxide synthase (eNOS), which is localized in the cholesterol-rich plasmalemmal microdomains involved in signal transduction, known as caveolae. The present study was undertaken to evaluate the effect of hypercholesterolemia and fatty streak formation on the endothelial caveolae and on endothelial function, and attempted to determine to what extent the caveolae were involved in endothelium-derived NO production. METHODS AND RESULTS: We first studied the effect of atheroma on endothelial NO production. Fatty streak infiltrated aorta of cholesterol-fed New Zealand White rabbits demonstrated an impairment of acetylcholine-induced relaxation and nearly normal calcium ionophore A23187-induced maximal relaxation. The abundance of caveolae in the endothelium covering the fatty streak, as well as their 'grape-like' clustering, appeared to be decreased. We therefore investigated the effect, on endothelial NO production, of the cholesterol-binding agents 2-hydroxypropyl-beta-cyclodextrin (hp-beta-CD) and filipin, known to alter caveolae structure and/or function. Treatment with either hp-beta-CD (2%) or filipin (4 microg/ml) did not affect contraction to phenylephrine or relaxant responses to A23187 or to the NO donor sodium nitroprusside. In contrast, both treatments impaired acetylcholine-induced relaxation. Cultured bovine aortic endothelial cells (BAEC) similarly treated with hp-beta-CD demonstrated a 50% decrease of total cellular cholesterol and a decreased abundance of caveolae as well as their 'grape-like' clustering. Cholesterol depletion decreased the bradykinin-induced transient peak of free intracellular calcium and subsequent receptor-stimulated NO production (assessed using reporter cells rich in soluble guanylyl cyclase), whereas that elicited by A23187 remained unaltered. CONCLUSION: Fatty streak deposit is associated with a decrease in caveolae 'transductosomes' abundance which appears to represent a novel mechanism of endothelial dysfunction.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1997

Glomerular endothelial dysfunction determines disease progression: a hypothesis.

A glomerular endothelial function with its hemodynamic impact is proposed to determine disease progression. In the clinical settings associated with an intact endothelial function, such as minimal-change steroid-sensitive nephrosis, the early phase of diabetes mellitus and the early stage of an experimental model of renal ablation in animals, it was observed that adequate renal perfusion correlates with the intact structure and function of the nephron with no evidence of disease progression. In contrast, the clinical settings associated with endothelial dysfunction, such as chronic glomerulonephropathy, the late stage of diabetes mellitus and a renal ablation model in animals, are usually associated with a reduction in renal perfusion. The magnitude of renal hypoperfusion observed in all forms of chronic glomerulonephropathies is proportional to the degree of clinical severity. A progressive pattern of renal hypoperfusion is uniquely observed when disease severity progresses. In this context, a new therapeutic maneuver aiming to improve renal perfusion is proposed for treating glomerulonephropathy with disease progression and preventing it from developing to end-stage renal disease.

Animals↗