Occult Mönckeberg medial calcinosis of the facial and infraorbital arteries in an elderly edentulous patient.

Mönckeberg medial calcinosis (MMC) is a potentially serious vasculopathy involving calcification of the arterial tunica media of the extremities, heart, and other viscera. There are a limited number of cases reported in the dental literature, usually associated with the facial artery. Although MMC is often discerned as an occult radiologic finding in middle-aged adults, its presence may serve as a harbinger for end-stage renal disease, diabetes, other pathologic processes, and possible regional hypoperfusion. The objective of this report is to feature an elderly patient with MMC of the facial and infraorbital arteries. In addition, a brief review of published cases of MMC and its differential diagnosis have been provided. It is recommended that affected patients be referred for a comprehensive medical assessment. Timely discovery of calcified arteries may improve patient outcomes.

Arterioesclerosis de Monckeberg en vasos uterinos: un interesante hallazgo incidental / Arteriosclerose de Monckeberg nos vasos uterinos: um achado incidental interessante / Monckeberg arteriosclerosis in uterine vessels: an interesting incidental finding

Se realizó la comunicación de un caso clínico-patológico, diagnosticado en el Hospital Docente Clínico Quirúrgico "Joaquín Albarrán" de La Habana. En dicha entidad se presentó en una paciente femenina de 85 años de edad con antecedentes de diabetes mellitus tipo 2, ingresada por cuadro de insuficiencia arterial de miembro inferior izquierdo por lo cual se le realizan amputación supracondilia y al tercer día de su estadía hospitalaria, fallece. En la autopsia se arribó al diagnóstico anatomopatológico de arterioesclerosis de Mönckeberg de vasos del útero. Esta es una forma de arterioesclerosis muy relacionada con la senectud, pero factores de riesgo como diabetes mellitus y la enfermedad renal crónica pueden contribuir de forma directa en su desarrollo y progresión. Su diagnóstico es un hallazgo incidental en muestras histopatológicas(AU)

A clinical-pathological case was reported, diagnosed at the Joaquín Albarrán Clinical Surgical Teaching Hospital in Havana. In this entity, an 85-year-old female patient with a history of type 2 diabetes mellitus was presented, admitted due to arterial insufficiency of the lower left limb, for which she underwent supracondylar amputation and died on the third day of her hospital stay. At the autopsy, the pathological diagnosis of Mönckeberg arteriosclerosis of vessels of the uterus was reached. This is a form of arteriosclerosis closely related to old age, but risk factors such as diabetes mellitus and chronic kidney disease can directly contribute to its development and progression. Its diagnosis is an incidental finding in histopathological samples(AU)

Um caso clínico-patológico foi relatado, diagnosticado no Hospital de Clínica Cirúrgica "Joaquín Albarrán" em Havana. Nessa entidade, apresentou-se uma paciente de 85 anos, com história de diabetes mellitus tipo 2, internada por insuficiência arterial do membro inferior esquerdo, para a qual sofreu amputação aupracondiliana e faleceu no terceiro dia de internação. Na autopsia, o diagnóstico patológico da arteriosclerose de Mönckeberg de navios do útero foi conseguido. Essa é uma forma de arteriosclerose intimamente relacionada à velhice, mas fatores de risco como diabetes mellitus e doença renal crônica podem contribuir diretamente para seu desenvolvimento e progressão. Seu diagnóstico é um achado incidental em amostras histopatológicas(AU)

Media sclerosis drives and localizes atherosclerosis in peripheral arteries.

Media sclerosis (MS) and peripheral artery disease (PAD) may coincide, particularly in type 2 diabetics (T2D) and in patients with chronic kidney disease (CKD). In contrast to non-diabetics, in T2D PAD is more severe and more distal. Although MS is suspected to play a role, the underlying pathophysiological reasons for the differences still remain elusive today. We tested the hypothesis that MS is a promoter of atherosclerosis as it occurs in T2D with PAD by interfering with arterial remodeling using an in-silico simulation. We confirmed that MS aggravates PAD by promoting negative remodeling. We found that the effect is more pronounced in smaller distal arteries compared to larger proximal ones. Our results suggest that the degree of this divergence depends on the ratio between the thickness of the intima relative to the thickness of the media/adventitia of the individually affected arteries.

Missense mutation of VKORC1 leads to medial arterial calcification in rats.

Vitamin K plays a crucial role in the regulation of vascular calcifications by allowing activation of matrix Gla protein. The dietary requirement for vitamin K is low because of an efficient recycling of vitamin K by vitamin K epoxide reductase (VKORC1). However, decreased VKORC1 activity may result in vascular calcification. More than 30 coding mutations of VKORC1 have been described. While these mutations have been suspected of causing anticoagulant resistance, their association with an increase in the risk of vascular calcification has never been considered. We thus investigated functional cardiovascular characteristics in a rat model mutated in VKORC1. This study revealed that limited intake in vitamin K in mutated rat induced massive calcified areas in the media of arteries of lung, aortic arch, kidneys and testis. Development of calcifications could be inhibited by vitamin K supplementation. In calcified areas, inactive Matrix Gla protein expression increased, while corresponding mRNA expression was not modified. Mutation in VKORC1 associated with a limited vitamin K intake is thus a major risk for cardiovascular disease. Our model is the first non-invasive rat model that shows spontaneous medial calcifications and would be useful for studying physiological function of vitamin K.

Mechanisms of Arterial Calcification: The Role of Matrix Vesicles.

Vascular calcification is related to vascular diseases, for example, atherosclerosis, and its comorbidities, such as diabetes and chronic kidney disease. In each condition, a distinctive histological pattern can be recognised that may influence technical choices, possible intra-operative complications, and procedure outcomes, no matter if the intervention is performed by open or endovascular means. This review considers the classification and initiating mechanisms of vascular calcification. Dystrophic and metastatic calcifications, Monckeberg's calcification, and genetic forms are firstly outlined, followed by their alleged initiation mechanisms; these include (a) ineffective macrophage efferocytosis; (b) ectopic osteogenesis driven by modified resident or circulating osteoprogenitors. As in physiological bio-mineralisation, active calcification starts with the deposition of cell derived matrix vesicles into the extracellular matrix. To substantiate this belief, an in depth ultra-structural documentation of hydroxyapatite crystal deposition on such vesicles is provided in an ex-vivo human vascular cell model. Revealing the vesicle composition and phenotype in normal and pathological vascular conditions will be essential for the development of new therapeutic strategies, in order to prevent and treat vascular calcification.

Mönckeberg medial calcinosis of the infraorbital arteries: a first case report.

Mönckeberg medial calcinosis describes calcifications affecting only the tunica media of medium-sized arteries. The entity is strongly associated with chronic kidney disease and diabetes mellitus. Radiographically, medial calcinosis presents as areas of linear calcifications in soft tissue; the linear calcifications are referred to as "tram tracks," "pipe stem," "rail tracking," or "tram line" when the affected vessel is viewed longitudinally. In oral and maxillofacial radiology, it is generally an incidental finding of the facial artery. In this article, we review the literature of Mönckeberg medial calcinosis and its clinical significance related to systemic diseases; we also present a case of Mönckeberg medial calcinosis of the head and neck that affects the facial arteries, internal carotid arteries, and infraorbital arteries. We believe this is the first presentation in the literature of Mönckeberg medial calcinosis visualized in the infraorbital arteries.

[АRTERIAL PRESSURE ON THE FIRST TOE AS A PROGNOSIS CRITERION OF THE COMPLICATION OCCURRENCE IN THE DIABETIC FOOT SYNDROME ON BACKGROUND OF MENKEBERG'S SCLEROSIS].

In the patients, suffering diabetes mellitus type ІІ, treated in 2015 - 2016 yrs for complicated diabetic foot syndrome, a systolic arterial pressure (SAP) on level of the first toe was determined, and roentgenography of the foot in two projections done. The SAP value from 120 to 200 mm Hg and higher have had witness the presence of Menkeberg?s sclerosis stages III - V. Prognostically favorable is a SAP value of 80 mm Hg and higher, and unfavorable data ­ the SAP value lowering lesser than 80 mm Hg. The SAP value lower than 30 mm Hg have had witness the vessel obliteration and thrombosis occurrence.

Medial Arterial Calcification: An Overlooked Player in Peripheral Arterial Disease.

Peripheral arterial disease (PAD) is a global health issue that is becoming more prevalent in an aging world population. Diabetes mellitus and chronic kidney disease are also on the increase, and both are associated with accelerated vascular calcification and an unfavorable prognosis in PAD. These data challenge the traditional athero-centric view of PAD, instead pointing toward a disease process complicated by medial arterial calcification. Like atherosclerosis, aging is a potent risk factor for medial arterial calcification, and accelerated vascular aging may underpin the devastating manifestations of PAD, particularly in patients prone to calcification. Consequently, this review will attempt to dissect the relationship between medial arterial calcification and atherosclerosis in PAD and identify common as well as novel risk factors that may contribute to and accelerate progression of PAD. In this context, we focus on the complex interplay between oxidative stress, DNA damage, and vascular aging, as well as the unexplored role of neuropathy.

Arteriosclerosis: facts and fancy.

Arterial vascular diseases comprise the leading cause of death in the industrialized world. Every physician learns about the pathology of these diseases in medical school. All pathologists evaluate arterial disease in surgical pathology and/or autopsy specimens. All clinicians encounter patients with clinical manifestations of these diseases. With such a common and clinically-important group of entities one would think there would be a general understanding of the "known" information that exists. That is, physicians and scientists should be able to separate what is fact and what is fancy. This review article is intended to generate thought in this regard.

Medial vascular calcification revisited: review and perspectives.

Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.

Role of sodium thiosulfate therapy in the treatment of digital necrosis due to Mönckeberg sclerosis.

Accelerated vascular calcification is a well-described complication of chronic kidney disease often affecting large and small vessels alike through a variety of mechanisms. Accordingly, dysregulation of calcium and phosphate balance, vitamin D metabolism, hyperparathyroidism, and endothelial injury can lead to both macrovascular and microvascular complications. We describe a 56-year-old Hispanic male with a history of end-stage renal disease, diabetes mellitus type 2, and medical noncompliance who developed sequential digital ischemia and necrosis involving both hands as well as right foot as a result of Mönckeberg sclerosis. An extensive metabolic and serologic workup was unrevealing but radiographic studies and histopathology revealed the diagnosis. A multifaceted approach was instituted including wound debridement and amputations along with intensive medical support. In addition to improving hypertensive control and striving for improved calcium and phosphate balance, sodium thiosulfate solution was administered for more than 1 year. This aggressive approach allowed his wounds to heal and has arrested further digital ischemia from occurring.

High glucose concentration does not modulate the formation of arterial medial calcification in experimental uremic rats.

High phosphate-induced phenotypic switching of smooth muscle cells (SMCs) into osteogenic cells is critical for the formation of arterial medial calcification in chronic kidney disease. Because vascular calcification is also prevalent in type 2 diabetes, we examined whether glucose concentration affects high phosphate-induced SMC phenotypic switching and calcification. First, the formation of arterial medial calcification was compared among 4 groups: adenine-fed uremic rats, streptozotocin-injected hyperglycemic rats, adenine-fed and streptozotocin-injected uremic/hyperglycemic rats, and control rats. Calcification was obvious in uremic and uremic/hyperglycemic rats, whereas it was undetectable in the others. Aortic calcium contents were significantly elevated in uremic and uremic/hyperglycemic rats, but they were not different between the two groups. Moreover, hyperglycemia had no effects on the reduced expression of SMC differentiation markers including smooth muscle α-actin and SM22α and on the increased expression of osteogenic markers, such as Runx2, in uremic rats. Second, cultured SMCs were incubated in the medium with various concentrations of phosphate (0.9-4.5 mmol/l) and glucose (5-50 mmol/l), and calcium deposition was measured. Although high phosphate dose-dependently increased calcium contents, they were unaffected by glucose concentration. Results suggest that glucose concentration does not directly modulate high phosphate-induced SMC phenotypic switching and arterial medial calcification.

[Mönckeberg's sclerosis -- crystal-induced angiopathy]. / Mönckeberg-sclerosis -- kristály indukálta angiopathia.

INTRODUCTION: Mönckeberg's sclerosis is a special form of arteriosclerosis characterized by calcification and ossification of the media of medium size arteries mainly of lower extremities. AIMS: The aim of the authors was to examine medium size arteries with Mönckeberg's sclerosis in 22 amputated lower legs of 16 patients in order to demonstrate different crystals in the wall of blood vessels. METHODS: The methodology was based on previous findings of the authors indicating that in different metabolic disorders many crystals remain demonstrable in unstained histological sections unlike in haematoxylin-eosin stained sections. RESULTS: In unstained sections the authors observed rhomboid or prismatic calcium pyrophosphate dihydrate and clusters of elongated narrow hydroxyapatite crystals in the wall of medium size arteries of all examined cases. Both types of crystals showed axis parallel positive birefringence under polarized light. The intensity of birefringence of hydroxyapatite crystals was weaker in comparison with that of calcium pyrophosphate dihydrate crystals. Occasionally, other crystals which were different in shape from both calcium pyrophosphate dihydrate and hydroxyapatite crystals were also observed. CONCLUSIONS: It seems likely that similarly to crystal deposition induced arthropathy, calcium pyrophosphate dihydrate, hydroxyapatite and other crystals cause fibrosis and intimal proliferation, which may contribute to progressive occlusion of blood vessels resulting in ischemic symptoms. Based on this observation Mönckeberg's sclerosis may be defined as a crystal-induced angiopathy.

Amplification of atherosclerotic calcification and Mönckeberg's sclerosis: a spectrum of the same disease process.

Autopsy studies have shown the near universal presence of fatty streaks and fibroatheromas in the general population from which chronic kidney disease (CKD) patients arise. The vast majority of CKD patients have multiple conventional cardiovascular risk factors. Atherosclerosis, once present, can predominantly manifest as medial calcification, which has been previously termed Mönckeberg's sclerosis. This term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathological diagnosis and treatment of CKD bone and mineral disorder. Factors that appear to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxy vitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in CKD patients and may be future targets for diagnosis and treatment. Although conventional atherosclerotic risk factors should be optimally managed, it should be noted that trials of hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification as measured by computed tomography scans.

Media calcification and intima calcification are distinct entities in chronic kidney disease.

Calcification of the vascular tree is common in physiologic and pathologic conditions, i.e., aging, diabetes, dyslipidemia, genetic diseases, and diseases with disturbances of calcium metabolism. In chronic kidney disease, vascular calcification is even more common, develops early, and contributes to the markedly increased cardiovascular risk in this particular population. Pathomorphologically, atherosclerosis (i.e., plaque-forming degenerative changes of the aorta and of large elastic arteries) and arteriosclerosis (i.e., concentric media thickening of muscular arteries) can be distinguished. Increasing knowledge about calcification together with improved imaging techniques provided evidence that also vascular calcification has to be divided into two distinct entities according to the specific sites of calcification within the vascular wall: Patchy calcification of the intima in the vicinity of lipid or cholesterol deposits as present in plaque calcification and calcification of the media in the absence of such lipid or cholesterol deposits, known as Mönckeberg-type atherosclerosis. The two types of calcification may vary according to the type of vessel (large elastic versus smaller muscular type artery) and proximal versus distal sites of the arterial tree. Furthermore, clinical studies showed that it is not purely academic to distinguish between intimal and medial calcification but rather relevant for the clinical presentation, treatment, and prognosis because each type leads to different clinical consequences. In vivo studies in animal models provided evidence in favor of common pathomechanisms between vascular calcification and atherosclerosis; however, there is other, strong experimental and clinical evidence that pleads for the continued distinction between intimal and medial calcification.

Accelerated atherosclerotic calcification and Monckeberg's sclerosis: a continuum of advanced vascular pathology in chronic kidney disease.

Autopsy studies have demonstrated the near universal presence of fatty streaks and fibroatheromas in the general population from which patients with chronic kidney disease (CKD) arise. The vast majority of patients with CKD have multiple conventional cardiovascular risk factors. Vascular atherosclerotic calcification develops in most patients as they transition from the general population to significant CKD as part of cholesterol crystallization within atherosclerotic lesions. Once present, however, atherosclerotic medial calcification can become prominent and has been previously identified as Mönckeberg's sclerosis. A unifying concept supported by the preponderance of pathologic evidence contends that Mönckeberg's sclerosis is a manifestation of accelerated atherosclerosis in patients with CKD. The term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathologic diagnosis and treatment of CKD bone and mineral disorder. Factors that seem to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxyvitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in patients with CKD and may be future targets for diagnosis and treatment because randomized trials with hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification.