Arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg: qual a diferença? / Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?

Resumo A principal causa de óbito na contemporaneidade são as doenças cardiovasculares. Arteriosclerose, aterosclerose, arteriolosclerose e arteriosclerose de Monckeberg são termos frequentemente utilizados como sinônimos, mas traduzem alterações distintas. O objetivo desta revisão foi discutir os conceitos de arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg. O termo arteriosclerose é considerado mais genérico, significando o enrijecimento e a consequente perda de elasticidade da parede arterial, abarcando os demais tipos. A aterosclerose é uma doença inflamatória secundária a lesões na camada íntima, que tem como principal complicação obstrução crônica e aguda do lúmen arterial. A arteriolosclerose se refere ao espessamento das arteríolas, particularmente relacionada à hipertensão arterial sistêmica. Já a esclerose calcificante da média de Monckeberg designa a calcificação, não obstrutiva, da lâmina elástica interna ou da túnica média de artérias musculares. As calcificações vasculares, que incluem lesões ateroscleróticas e a esclerose calcificante da média de Monckeberg, vêm sendo estudadas como um fator de risco para a morbimortalidade cardiovascular.

Abstract Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Peripheral arterial stiffness is correlated with intrarenal arteriolosclerosis according to biopsies from patients with kidney disease.

AIM: To investigate the possible associations between intrarenal arteriolosclerosis as determine by renal biopsy and endothelial function as well as arterial stiffness measured by peripheral arterial tonometry (EndoPAT). METHODS: This was a cross-sectional study. Patients who underwent both renal biopsy and EndoPAT were recruited, and intrarenal arteriolosclerosis was graded according to the pathological slice. Endothelial function and arterial stiffness were both measured by EndoPAT and were expressed by the reactive hyperemia index (RHI) and augmentation index (AIx), respectively. AIx@75, representing the AIx standardized to a heart rate of 75 bpm was also determined. RESULTS: In total, 113 patients were assessed, the mean age was 51 ± 13, and 68.1% were men. The natural logarithm RHI (LnRHI), AIx and AIx@75 were significantly different among different grades of intrarenal arteriolosclerosis (P = .030, P < .001, P < .001, respectively). In the multivariable adjusted model, for every SD increase in the AIx and AIx@75, the odds of having more severe arteriolosclerosis were 2.506 times (95% confidence interval [CI] 1.464-4.288, P = .001] and 3.191 times (95% CI 1.780-5.719, P < .001) higher, respectively, and the association between the LnRHI and intrarenal arteriolosclerosis was nullified (P = .059). The positive values of the AIx and AIx@75 for the diagnosis of severe intrarenal arteriolosclerosis were 0.80 (95% CI 0.73-0.88, P < .001) and 0.78 (95% CI 0.70-0.87, P < .001), respectively. CONCLUSION: Subjects with more severe intrarenal arteriolosclerosis have greater peripheral vascular stiffness; AIx and AIx@75 reflected peripheral vascular stiffness could be used to identify patients with severe intrarenal arteriolosclerosis.

Intrarenal resistive index conundrum: systemic atherosclerosis versus renal arteriolosclerosis.

Background: We aimed to evaluate the relationship between biopsy-proven kidney lesions, subclinical markers of atherosclerosis and intrarenal resistive index (RRI) in chronic kidney disease (CKD) patients. Methods: This cross-sectional, single-center study prospectively enrolled 44 consecutive CKD patients (57% male gender, 54.1 (95%CI, 49.7-58.6) years, median eGFR 28.1 (15.0-47.7) mL/min) diagnosed by renal biopsy during 6 months in our clinic. RRI, carotid intima-media thickness (IMT), Kauppila score for abdominal aortic calcification (AACs) were assessed. Traditional and nontraditional atheroscleosis risk factors were also evaluated. Results: Most of the patients had a diagnosis of glomerular nephropathy, with IgA nephropathy and diabetic nephropathy being the most frequent. RRI increased proportionally with CKD stages. Patients with RRI >0.7 (39%) were older, had diabetic and vascular nephropathies more frequently, higher mean arterial blood pressure, increased systemic atherosclerosis burden (IMT and AACs), higher percentage of global glomerulosclerois, GBM thickness, arteriolosclerosis and interstitial fibrosis/tubular atrophy. RRI directly correlated with age (rs = 0.55, p < 0.001) and with all the studied atherosclerosis markers (clinical atherosclerosis score rs = 0.50, p = 0.02; AACs rs = 0.50, p < 0.01; IMT rs = 0.34, p = 0.02). Also, global glomerulosclerosis (rs = 0.31, p = 0.03) and interstitial fibrosis/tubular atrophy (rs = 0.35, p = 0.01) were directly correlated with RRI. In multivariable adjusted binomial logistic regression models, only arteriolosclerosis was retained as independent predictor of RRI >0.7. Conclusion: The analysis of RRI may be useful in the evaluation of the general vascular condition of the patient with CKD, supplying information about both microvascular and macrovascular impairment. Moreover, RRI correlates well with renal histopathologic characteristics, particularly with arteriolosclerosis.

Relationship Between Type of Hypertension and Renal Arteriolosclerosis in Chronic Glomerular Disease.

BACKGROUND/AIMS: Hypertension (HT) is a common complication in patients with chronic kidney disease (CKD). However, the relationship between circadian rhythm disorder of blood pressure (BP) and intra-renal damage remains unclear. METHODS: Ninety patients with chronic glomerular disease (CGD) were included in the present study. On the basis of the clinic BP (CBP) and 24 h-ambulatory BP (ABP) measurements, the patients were divided into the following groups; normotension (NT), white coat HT (WHT), masked HT (MHT), and sustained HT (SHT). For renal histopathological assessment, we evaluated each biopsy specimen for sclerotic glomeruli (SG), interstitial fibrosis (IF), intimal thickening of intra-lobular arteries (ILA), and arteriolar hyalinosis (AH). RESULTS: The prevalence of NT, WHT, MHT and SHT was 60.0%, 3.3%, 23.3%, and 13.4%, respectively. Compared with circadian BP pattern, all-day HT was most prevalent in the SHT group, whereas nighttime HT was most prevalent in the MHT group. The results of histological analysis showed that the SHT group had more severe SG and IF and the MHT group had more severe IF compared to the NT group. As for renal arteriolosclerosis, the MHT and SHT groups had more severe AH compared with the NT group, whereas ILA was comparable among all four groups. Furthermore, multivariate analysis revealed that ILA was significantly correlated only with age, whereas AH was significantly correlated with age and HT based on ABP, but not HT based on CBP. CONCLUSIONS: Our findings suggest that renal AH was severe not only in the SHT group, but also in the MHT group. Careful ABP monitoring should be recommended in patients with CGD.

Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction.

Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-ß and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-ß and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11-25, 26-50, 51-75, and 76-150 µm), TGF-ß, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11-25 and 26-50 µm diameters parallel to TGF-ß overexpression. In gastrocnemius muscle, the number of arterioles/mm(2) was only increased in the 11 to 25 µm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-ß and downregulation of angiostatin in MI rats.

Tacrolimus reduction with everolimus addition for calcineurin inhibitor-induced arteriolopathy in kidney allografts.

AIM: The aim of this study was to evaluate the effect of tacrolimus (TAC) reduction with everolimus (EVR) addition on the maintenance immunosuppression for the recipients with calcineurin inhibitor arteriolopathy (CNIA). METHODS: This retrospective study consisted of 13 kidney allograft recipients who were found to have CNIA on protocol biopsy specimens. The time of intervention was 9-89 months. All the patients were on TAC, mycophenolate mofetil (MMF). 9 of 13 were on steroid. EVR was added and TAC dose was reduced. MMF dose was not changed. Revaluation biopsy was taken 12 months after the intervention. TAC trough levels (TACC0 , ng/mL), EVR trough levels (EVRC0 , ng/mL), estimated glomerular filtration rate (eGFR, mL/min), and urine protein per creatinine (uP/Cr, g/g creatinine) were compared before and 1 year after intervention. Changes in pathological findings and adverse events were also reviewed. RESULTS: Aah scores improved in 5 patients. Aah scores did not change in the rest of the patients. No deterioration was observed. No improvement was seen in those with aah3. TACC0 reduced from 3.3 to 2.3. EVRC0 at revaluation was 4.1. eGFR improved from 44.3 to 49.8. uP/Cr slightly increased from 0.20 to 0.26. EVR was discontinued in 1 patient due to an adverse event. EVR dose was reduced in 5 patients due to adverse events. CONCLUSION: TAC reduction with EVR addition improves CNIA histologically in selected cases.

Relationship between vascular function indexes, renal arteriolosclerosis, and renal clinical outcomes in chronic kidney disease.

AIM: Hypertension contributes critically to the development of renal arteriolosclerosis in chronic kidney disease (CKD), but the impact of vascular function indexes including central blood pressure on renal arteriolosclerosis has not been investigated. We determined whether vascular function indexes were related to renal arteriolosclerosis and renal clinical outcomes in CKD. METHODS: This cross-sectional study was implemented in our hospital. Subjects were in-patients with CKD aged ≥20 years who underwent a renal biopsy. Vascular function indexes included central systolic blood pressure (SBP), cardio-ankle vascular index (CAVI), and renal resistive index. Central SBP was measured non-invasively using an automated device. Arteriolosclerosis was assessed histologically. Renal clinical outcomes included estimated glomerular filtration rate using serum creatinine (eGFRcreat) or cystatin C (eGFRcys), and the urinary albumin-creatinine ratio. RESULTS: Among vascular function indexes, central SBP was weakly correlated with renal arteriolosclerosis (n = 55). Renal arteriolosclerosis was increased in hypertensive or hyperuricaemic patients, and negatively correlated with serum high-density lipoprotein (HDL) cholesterol and eGFRcys, which were independent risk factors for renal arteriolosclerosis in a stepwise multivariate regression analysis. Of the vascular function indexes, CAVI showed the strongest correlation with all renal clinical outcomes. Central SBP was correlated with only urinary albumin-creatinine ratio, while renal resistive index was correlated with eGFRcreat and urinary albumin-creatinine ratio. CONCLUSION: Decreased serum HDL cholesterol was independently and most closely associated with renal arteriolosclerosis. Of the vascular function indexes, CAVI had the greatest impact on renal clinical outcomes, although it was not associated with renal arteriolosclerosis.

Blood-brain barrier dysfunction and cerebral small vessel disease (arteriolosclerosis) in brains of older people.

The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.

[Outcomes of hybrid operations in multi storeyed lesions of arteries of the aortoiliac and femoropopliteal segments].

The work was aimed at analysing immediate and remote outcomes of hybrid operations in storey atherosclerotic lesions of the aortoiliac and femoropopliteal segments. Over the period from 1997 to 2012 hybrid operations were performed in a total of 224 patients presenting with multi-storeyed lesions of iliac and lower-limb arteries, classified as TASC A, B, C, and D. The operations were carried out at departments of vascular surgery of Clinical Hospital No 83 of the Federal Biomedical Agency of Russia and the Centre of Cardiovascular and Endovascular Surgery of Clinical Hospital No 119 of the Federal Biomedical Agency of Russia. All operations were simultaneous. The patients were subdivided into groups according to the character of intervention on iliac arteries: 1 - balloon angioplasty of iliac arteries, 2 - stenosing of iliac arteries, 3 - loop endarterectomy from iliac arteries followed by implantation of a covered stent into the zone of rupture of the intimal cylinder. In all cases the interventions of the arteries of the aortoiliac segment were combined with various open surgical reconstructions of the femoropopliteal segment. Technical success amounted to 99.1%. Interventional complications of the endovascular stage requiring conversion occurred in 2 cases. The immediate period complications influencing patency of the reconstructions performed were noted in 10 (4.5%) patients. Patency on the hospital stage with the deduction of cases of technical failures amounted to 98.6%. The remote results were followed up during 5 years in 76.5% of patients. Five-year primary assisted patency of the aortoiliac zone amounted to: in group 1 - 79.2%, in group 2 - 77.9%, and in group 3 - 89.4%. Five-year assisted patency of the femoropopliteal segment amounted to: for EAE of the common femoral artery - 98.2%, for profundoplasty - 100%, femoral proximal popliteal bypass grafting - 77.3%, femoral distal popliteal bypass grafting - 74.1%, femoral-tibial bypass grafting - 61.4%. There were no statistically significant differences in patency of the reconstructions of the femoropopliteal segment depending upon the type of intervention on the aortoiliac segment.

Effects of deranged glucose homeostasis on peripheral arterial stiffness index in patients with pre-diabetes mellitus.

Premature arteriosclerosis may be one of the mechanisms linking pre-diabetes mellitus (pre-DM) and cardiovascular disease. We sought to characterize premature arteriosclerosis in pre-DM using different arterial stiffness indices and to find the independent contributors of this process. We recruited 33 patients without DM, 53 patients with pre-DM, and 34 subjects with DM. Both the compliance index (CI) and stiffness index (SI) were measured. Patients with pre-DM and DM had lower CI (3.8 ± 2.1 versus 5.2 ± 3.0 units; P < 0.05 and 3.6 ± 1.8 versus 5.2 ± 3.0 units; P < 0.05, respectively) and higher SI (8.0 ± 2.0 versus 6.7 ± 1.6 m/s; P < 0.01 and 9.4 ± 2.3 versus 6.7 ± 1.6 m/s; P < 0.001, respectively) than patients without DM. Using multivariate linear regression analysis, age, heart rate, and HOMA index were independent determinants for SI (whole model: R(2) = 0.47, P < 0.001), whereas male gender, hsCRP, and HOMA index were independent determinants for CI (whole model: R(2) = 0.34, P < 0.01). The HOMA index was an independent determinant for arterial stiffness. Increased insulin resistance may associate with increased arterial stiffness at peripheral arteries in pre-DM patients.

[Arteriolosclerosis and atherosclerosis. Pathology of the distal and proximal arterial bed. Pathogenesis of diabetic microangiopathy].

Microangiopathy (MAP) in the distal arterial bed develops in the structures high in pericytes that have myofibrils and, by interacting with the endothelium, form the first peristaltic pumps; they push lymph, hemolymph and blood from the arterial bed to the venous one. The role of glucose, hyperglycemia, a glycation reaction and its end products in microvascular interstitial tissue damage in the arterial bed is shown only in the neuron axon terminals that surround the pool of the intercellular medium while the other axonal parts are present in the cerebrospinal fluid pool where hyperglycemia is absent. When glucose metabolism is activated through the poliolovic pathway, the endothelial cytosole accumulates organic osmolytes, such as sorbitol alcohol that, by causing hyperhydration, increases the height of endothelial cells. The decreased lumen of arterioles and capillaries enhances peripheral resistance to blood flow to give rise hypoperfusion and chronic hypoxia. Moreover, by bypassing the exchange capillaries and worsening cellular hypoperfusion and hypoxia in the paracrine communities, the arteriolo-venular shunt that releases blood into the venous bed functions, by getting around the exchange capillaries. Glucose metabolism activation through the hexosamine pathway generates glycotoxins, such as glyoxal and methylglyoxal. As bifunctional reagents, they interact with proteins simultaneously, by using both ends, form cross-links between the collagen fibers in the vascular interstitial matrix and irreversibly enhance the rigidity of arteriolar and capillary walls. As the rigidity of the walls is increased, the pericytes are unable to move blood along the capillaries, by worsening hypoperfusion and hypoxia. In diabetes, hyperglycemia becomes persistent and glycation increased. The conversion of collagen structured in the vascular wall to glycosylation end products and the impaired biological function of endoecology are a cause of a biological reaction of interstitial tissue inflammation. The obligate part of the biological reaction of inflammation is the oxidation by reactive oxygen species and the generation of malondialdehyde, that is also a bifunctional reagent. Fibroblast proliferation and arteriosclerosis are a result of MAP as a destructive inflammatory process in the arteriolar and capillary walls.

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease.

Hypertension has an important function in the formation of renal arterio-arteriolosclerosis. However, renal arterio-arteriolosclerosis is sometimes found in biopsy specimens of normotensive patients, which indicates unknown factors may contribute to renal arterio-arteriolosclerosis. In this study, we aimed to evaluate the effects of glucose metabolism/insulin resistance on renal arterio-arteriolosclerosis. Forty-eight patients with biopsy-proven non-diabetic chronic glomerular disease were included. Renal arterio-arteriolosclerosis was evaluated as the percentage of vessels showing hyaline changes or wall thickening. We correlated renal arterio-arteriolosclerosis with clinical parameters including indices obtained by 75 g oral glucose tolerance test. Of the 48 patients, 30 had hypertension. The results of univariate analysis showed significant association of renal arterio-arteriolosclerosis with hypertension, increased serum creatinine (S-Cr), hypertriglyceridemia, increased 2-h plasma glucose (PG) and increased 2-h plasma insulin (PI). In stepwise multiple regression analysis, hypertension (beta=0.344, P=0.009), S-Cr (beta=0.287, P=0.03) and 2-h PG (beta=0.274, P=0.03) were independently associated with renal arterio-arteriolosclerosis. Eleven of the 30 hypertensive patients did not have renal arterio-arteriolosclerosis. The hypertensive patients with renal arterio-arteriolosclerosis showed significantly higher 2-h PG (134+/-25 vs. 106+/-26 mg per 100 ml, P=0.008) and higher 2-h PI (67.7+/-34.9 vs. 48.3+/-30.0 microU ml(-1), P=0.04) compared with those without renal arterio-arteriolosclerosis, but the difference in S-Cr was not significant. Postprandial hyperglycemia and hyperinsulinemia may contribute to the formation of renal arterio-arteriolosclerosis independently of hypertension.

Lead, at low levels, accelerates arteriolopathy and tubulointerstitial injury in chronic kidney disease.

Chronic lead exposure has been epidemiologically linked with hypertension and renal disease. Clinical studies suggest that low lead levels may contribute to renal progression. However, experimental studies have not examined whether low levels of lead accelerate progression in experimental chronic renal disease. Sprague-Dawley rats were administered lead (L; 150 ppm in drinking water, n = 16) for 4 wk, followed by remnant kidney (RK) surgery with continuation of lead for an additional 12 wk; control rats (n = 9) were treated similarly but did not receive lead. Lead treatment was well tolerated and resulted in modest elevations in whole blood lead levels (26.4 +/- 4.5 vs. 1 +/- 0 mug/dl, week 16, P < 0.001). Lead treatment was associated with higher systolic blood pressure (P < 0.05) and worse renal function (creatinine clearance 1.4 +/- 0.4 vs. 1.8 +/- 0.5 ml/min, RK+L vs. RK, P < 0.05), and with a tendency for greater proteinuria (6.6 +/- 6.1 vs. 3.6 +/- 1.5 mg protein/mg creatinine, RK+L vs. RK, P = 0.08). While glomerulosclerosis tended to be worse in lead-treated rats (37.6 +/- 11 vs. 28.8 +/- 2.3%, RK+L vs. RK, P = 0.06), the most striking finding was the development of worse arteriolar disease (P < 0.05), peritubular capillary loss (P < 0.05), tubulointerstitial damage, and macrophage infiltration (P < 0.05) in association with significantly increased renal expression of monocyte chemoattractant protein-1 mRNA. In conclusion, lead accelerates chronic renal disease, primarily by raising blood pressure and accelerating microvascular and tubulointerstitial injury.

Cambios estructurales y calcificaciones vasculares en la uremia / No disponible

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