Human Arteriosclerosis Research Articles

Transcriptomics Analysis Revealed Key Genes Associated with Macrophage Autophagolysosome in Male ApoE-/- Mice Aortic Atherosclerosis.

Atherosclerosis (AS) is the most common cause of cardiovascular and cerebrovascular diseases. However, the mechanisms underlying atherosclerotic plaque progression remain unclear. This study aimed to investigate the genes associated with the development of atherosclerosis in the aorta of ApoE-/- male mice, which could serve as novel biomarkers and therapeutic targets in interventions to halt plaque progression. Eight-week-old ApoE-/- mice were fed a normal purified laboratory diet or a Western Diet (WD) for 6 or 22 weeks. High-throughput sequencing technology was used to analyze the transcriptomes of the aortas of four groups of mice that were exposed to different dietary conditions. We retrieved and downloaded the human Arteriosclerosis Disease Chip dataset GSE100927 from the Gene Expression Omnibus (GEO) database and selected 29 cases of carotid atherosclerotic lesions and 12 cases of normal carotid tissues as the experimental and control groups, respectively, to further verify our dataset. In addition, we used quantitative reverse transcription polymerase chain reaction (QT-PCR) to verify the expression levels of the core genes in an atherosclerosis mouse model. There were 265 differentially expressed genes (DEGs) between the ApoE-/- Male mice AS22W group and Sham22W group. In addition to the well-known activation of inflammation and immune response, t the autophagy-lysosome system is also an important factor that affects the development of atherosclerosis. We identified five core genes (Atp6ap2, Atp6v0b, Atp6v0d2, Atp6v1a, and Atp6v1d) in the protein-protein interaction (PPI) network that were closely related to autophagosomes. Hub genes were highly expressed in the carotid atherosclerosis group in the GSE100927 dataset (P < 0.001). QT-PCR showed that the RNA level of Atp6v0d2 increased significantly during the development of atherosclerotic plaque in ApoE-/- male mice. Five core genes which affect the development of aortic atherosclerosis through the autophagy-lysosome system, especially Atp6v0d2, were screened and identified using bioinformatic techniques.

Assessment of arteriosclerosis based on multiscale cross approximate entropy of human finger pulse wave.

Arteriosclerosis is one of the diseases that endanger human health. There is a large amount of information in pulse wave signals to reflect the degree of arteriosclerosis. The degree of arteriosclerosis is assessed by analyzing pulse wave signal and calculating multi-scale entropy values. A method based on the multiscale cross-approximate entropy of the pulse wave of the human finger is proposed to assess the degree of arteriosclerosis. A total of 86 subjects were divided into three groups. The data of 1000 pulse cycles were selected in the experiment, and the multiscale cross-approximate entropy was calculated for the climb time and pulse wave peak interval. Independent sample t-test analysis gives the small-scale cross-approximate entropy of the two time series of climb time and pulse wave peak interval as p< 0.001 in Groups 1 and 2. The large-scale cross-approximate entropy of the two time series of climb time and pulse wave peak interval is p< 0.017 in Groups 2 and 3. Using the proposed algorithm, the results showed that the small-scale cross-approximate entropy of climb time and pulse wave peak interval could reflect the degree of arteriosclerosis in the human body from the perspective of autonomic nerve function. The large-scale cross-approximate entropy of climb time and pulse wave peak interval confirmed the effect of diabetes on the degree of arteriosclerosis. The results demonstrate the multiscale cross-approximate entropy is a comprehensive index to evaluate the degree of human arteriosclerosis.

Telemedicine in the management of hypertension: Evolving technological platforms for blood pressure telemonitoring.

The prevalence of hypertension is high and still increasing in almost all communities regardless of high, middle, or low income. The control rate remains low in most countries. Telemedicine offers possibilities to improve blood pressure control. The past two decades witnessed the fast evolving telecommunication from telephone transmission to smart mobile phone technology for telemedicine. There is some evidence from randomized controlled trials that telemonitoring improves blood pressure control. However, it requires co‐interventions. The emerging new technology may offer even more possibilities in telemonitoring and co‐interventions, for instance, an interactive platform between patients and health professionals for the management of hypertension. Telemedicine might ultimately change the situation of the unsatisfactory management of hypertension in many communities. It helps fully utilize antihypertensive treatment, the most effective cardiovascular prevention, to achieve the goal of ending atherosclerosis and arteriosclerosis in humans.

Development of a New Type of Atherosclerosis Detection Device

This paper describes how to develop a practical new type of atherosclerosis detection device, which can realize real-time measurement and analysis of human atherosclerosis. According to the mechanism of human atherosclerosis, the design objectives of the system are formulated to determine the construction of the platform. The system calculates the pulse wave velocity by measuring the pulse wave of human fingers and toes, adds four blood pressure measurements to the system design, calculates the ankle-brachial index, and comprehensively measures and analyses the degree of human arteriosclerosis.

A reporter for tracking the UPR in vivo reveals patterns of temporal and cellular stress during atherosclerotic progression

Progression of human arteriosclerosis is associated with and promoted by induction of the endoplasmic reticulum (ER) stress pathway known as the unfolded protein response (UPR). Most studies that assess UPR markers in atherosclerosis rely on methodologies that suffer from low signal sensitivity, nonspecific immunohistochemistry, or inability to resolve differences between cellular subsets. To accurately monitor the UPR independently of artifacts generated postmortem, we describe here the first in vivo reporter for ER stress during atherosclerosis. Mice transgenic for the fluorescent XBP-1 ER stress indicator Erai were bred onto the Ldlr(-/-) background and fed an atherogenic diet. Subsequently, ERAI fluorescence at aortic roots was quantified and colocalized with lesional cell type. We found that the ERAI fluorescent signal increased as a function of time on the atherogenic diet and, in advanced lesions, was found close to necrotic cores. The majority of ERAI fluorescence localized to macrophages, and to a lesser extent, to intimal smooth muscle cells and patches of endothelial cells. These mice provide a valuable tool to monitor activation of the UPR in atherosclerosis and will be useful for future studies investigating relationships between pharmacologic and genetic modulators of UPR and atherosclerosis.

Synergy of aldosterone and high salt induces vascular smooth muscle hypertrophy through up-regulation of NOX1

Aldosterone and excessive salt intake are obviously implicated in human arteriosclerosis. Aldosterone activates NADPH oxidase that induces superoxide production and cardiovascular cell hypertrophy. The activity of NADPH oxidase is influenced by the expression of its subunit, through which, vasoactive agents activate in the enzyme. Here, we show that aldosterone elicited overexpression of the NOX1 catalytic subunit of NADPH oxidase in the presence of high salt in A7r5 vascular smooth muscle cells. We also showed that NOX1 is a key subunit involved in physiological aldosterone-induced NADPH oxidase activation. Aldosterone dose-dependently increased NOX1 expression and NADPH activity, which subsequently caused superoxide over-production and A7r5 cell hypertrophy. However, aldosterone had little effect on any of NOX1, superoxide over-production and cell hypertrophy in NOX1 knock-down A7r5 cells. These results suggest that the aldosterone-induced effects are mainly generated through NOX1. Aldosterone-induced NOX1 over-expression was augmented by 145 mM sodium chloride, as compared with control medium containing 135 mM NaCl. However, NOX1 over-expression was not induced in the absence of aldosterone, even in the presence of 185 mM NaCl. The mineralocorticoid receptor antagonist, eplerenone, completely abolished NOX1 over-expression, indicating that aldosterone is essential for this process.

Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury

Thrombin and other proteinases exert vascular effects by activating the proteinase-activated receptors (PARs). The expression of PARs has been shown to be upregulated after balloon injury and in human arteriosclerosis. However, the relationship between the receptor upregulation and the alteration of vasomotor function remains to be elucidated. We herein demonstrated that the contractile responses to the PAR-1 and PAR-2 agonist were markedly enhanced in the rabbit femoral arteries after balloon injury. Neointimal thickening was established 4 wk after the injury. No histological change was observed in the sham operation, where the saphenous artery was ligated without any balloon injury. The contractile response to K(+) depolarization was significantly attenuated 1 wk after the injury and then partly recovered after 4 wk. Thrombin, PAR-1-activating peptide, trypsin, and PAR-2-activating peptide induced no significant contraction in the control. All these stimulants induced enhanced responses 1 wk after balloon injury. Such enhanced responses were seen 4 wk after the injury, except for thrombin. There was no change in the Ca(2+) sensitivity of the contractile apparatus as evaluated in the permeabilized preparations. PAR-1-activating peptide (100 mumol/l), but no other stimulants, induced an enhanced contraction in the sham operation. The expression of PAR-1 and PAR-2 slightly increased after the sham operation, whereas it markedly and significantly increased after balloon injury. Our observations suggest that balloon injury induced the receptor upregulation, thereby enhancing the contractile response before the establishment of vascular lesions. The local inflammation associated with the sham operation may also contribute to the receptor upregulation.

Inflammatory stimuli upregulate Rho-kinase in human coronary vascular smooth muscle cells

Recent studies have demonstrated that upregulated Rho-kinase plays an important role in the pathogenesis of arteriosclerosis and vasospasm in both animals and humans. However, little is known about the molecular mechanism(s) involved in the Rho-kinase upregulation. Since inflammatory mechanisms have been implicated in the pathogenesis of arteriosclerosis and vasospasm, we examined whether inflammatory stimuli upregulate Rho-kinase in vitro and in vivo. In cultured human coronary vascular smooth muscle cells (hcVSMC), inflammatory stimuli, such as angiotensin II and interleukin-1β, increased Rho-kinase expression (at both mRNA and protein levels) and function (as evaluated by the extent of the phosphorylation of the ERM (the ezrin/radixin/moesin) family, substrates of Rho-kinase) in a time- and concentration-dependent manner. The expression of Rho-kinase was inhibited by blockades of protein kinase C (PKC) (by either GF109253 or prolonged treatment with phorbol myristate acetate for 24 h) and an adenovirus-mediated gene transfer of dominant-active Iκ-B, suggesting an involvement of PKC and NF-κB in the intracellular signal transduction pathway for the Rho-kinase expression. Furthermore, coronary vascular lesion formation (characterized by medial thickening and perivascular fibrosis) induced by a long-term administration of angiotensin II was markedly suppressed in NF-κB –/– mice with reduced expression and activity of Rho-kinase in vivo. These results indicate that the expression and function of Rho-kinase are upregulated by inflammatory stimuli (e.g. angiotensin II and IL-1β) in hcVSMC with an involvement of PKC and NF-κB both in vitro and in vivo.

Radiographic features of aortic bulb/valve mineralization in 20 dogs.

The radiographic features of aortic bulb/valve mineralization in 20 dogs were reviewed. Extent, shape, number, and location of mineralization were recorded. Five of the dogs had additional alternate imaging examinations, including bone scintigraphy, echocardiography, and thoracic computed tomography. A necropsy was done on one dog, and the area of mineralization was evaluated using routine histology. The median age was 10 (mean 9.7; SD +/- 2.7) years. There were five males, seven neutered males, one female, and seven neutered females. The breeds were: Irish setter (6); rottweiler (7); chow-chow (1); miniature dachshund (1); borzoi (1); English setter (1); English springer spaniel (1); great Dane (1); and greyhound (1). Dogs with both right and left lateral radiographs (n = 17) had mineralization visible on both views, more conspicuously on the right lateral radiograph (n = 12). Aortic bulb mineralization was identified on the ventrodorsal radiograph of only one dog. On lateral radiographs, the aortic bulb mineralization was localized within the 4th intercostal space and in the craniodorsal quadrant of the cardiac silhouette. In nine of the dogs, there were complex or multiple mineralizations and in 11 dogs, there was a single curvilinear mineral opacity oriented in a caudoventral to craniodorsal direction. In all radiographs, the mineralization was in the expected position of the aortic bulb, and echocardiography (n = 4), spiral computed tomography (n = 2), and necropsy (n = 1) confirmed that the mineralization was within the aortic bulb. Clinical pathologic data of the dogs suggested no reason for metastatic mineralization. Exact etiopathogenesis of the lesions were not determined in this study. Based on the histologic findings in one dog, the mineralization seen in the aortic root is similar to a form of dystrophic mineralization called Monckeberg's calcific arteriosclerosis in humans. No clinical signs attributable to the mineralization were observed.

Direct interaction of the extracellular matrix protein DANCE with apolipoprotein(a) mediated by the kringle IV-type 2 domain.

Lipoprotein(a) [Lp(a)] consists of LDL and apolipoprotein(a), and has been shown to be a major, independent, risk factor for arteriosclerosis and thrombosis in humans. To further elucidate the (patho)physiological function(s) of Lp(a)/apo(a), we searched for new protein ligands, using the yeast two-hybrid system and employing the highly repetitive kringle IV type 2 (KIV-2) sequence from apo(a) as bait. The extracellular matrix protein DANCE [developmental arteries and neural crest epidermal growth factor (EGF)-like] recently implicated in atherogenesis was identified as an interactor. A direct physical interaction between DANCE and apo(a) was confirmed by co-purification of both recombinant proteins derived from culture supernatants of transiently transfected COS-1 cells. Furthermore, binding of human plasma-derived Lp(a) to recombinant DANCE was also observed. Finally, when monoclonal anti-apo(a) and polyclonal anti-DANCE antibodies were applied to tissue slices of atherosclerotic carotid artery, the two proteins were found to be co-localized in endothelial and smooth muscle cells, suggesting that they occur together in the arterial wall. However, as yet, the in vivo relevance and the possible functional role of this newly identified DANCE:Lp(a)/apo(a) interaction remains speculative.

Homocysteine and Arteriosclerosis

Homocysteine is an amino acid and a product of methionine metabolism that is metabolized through two different enzymatic pathways: transsulfuration and remethylation. Vitamin B6 is important in homocysteine transsulfuration, whereas folate and vitamin B12 play significant roles in homocysteine remethylation. The hyperhomocysteinemia offers an explanation for observations on human arteriosclerosis that are difficult to explain by the cholesterol/fat approach. However, hyperhomocysteinemia can influence cognitive functions in the elderly. The causes of hyperhomocysteinemia are inherited and acquired. The treatment of hyperhomocysteinemia varies with underlying cause; generally, vitamin supplementation (with folic acid and vitamins B6 and B12) is effective in reducing homocysteine concentrations. Also, specific recommendations, food fortification with folic acid, and preventive strategies in European countries (as in United States) are necessary to decrease cardiovascular morbidity and mortality.

The "galloping" history of intermittent claudication.

Intermittent claudication (IC) due to arterial occlusive disease was first diagnosed by the French veterinary surgeon Jean-François Bouley jeune in a horse drawing a cabriolet in the streets of Paris as early as 1831. The animal was repeatedly exercised and always started to limp with the hind legs at similar work loads. Autopsy revealed partially thrombosed aneurysm of the abdominal aorta and occlusions of both femoral arteries which were correctly identified as the cause of IC. In 1858 the famous neurologist Jean-Martin Charcot working at the Salpêtrière in Paris first discovered the condition in a patient, who was wounded by a bullet during the conquest of Algery and developed iliac artery aneurysm obliterated by a thrombus. He was aware of the first description in veterinary medicine. In Germany IC was also first mentioned in horses (Rademacher, 1838). 13 reports of patients were contributed by the neurologist Heinrich Erb in 1898 and 1904. Some interesting features of the phenomenon of IC like the amount of exercise necessary to provoke it, localization, social relevance, prolongation of the Achilles tendon reflex, decrease of maximal plantar flexion force of the foot and production of "Lewis factor p" are summarized. In human patients arteriosclerosis is the well recognized principal cause of arterial obstructions, in horses, however, the lesions are due to infection by the roundworm Strongylus vulgaris. In the fascinating life cycle the larvae migrate into the intima of small and large arteries and provoke aneurysms and intravascular thrombosis.

Spontaneous Elastic Tissue Lesions in the Rat Abdominal Aorta, a Genetically Determined Phenotype

In this study, phenotypic expression of spontaneous elastic laminae defects within the rat abdominal aorta was examined. Lesions in Brown Norway (BN) rats were compared with those of New Zealand genetically hypertensive (GH) rats. BN and GH rats were cross-bred to determine the phenotypic expression of these lesions in successive F₁ and F₂ generations. Lesions were assessed by distribution, number and a semiquantitative index of severity. All BN aortae contained numerous elastic tissue defects. In comparison, GH aortae contained only occasional elastic tissue lesions. F₁ aortae contained lesions in numbers similar to those of the parental BN strain; however, F₁ lesions were of significantly greater severity. Within the F₂ generation, a wide range in both lesion numbers and severity indices was observed, with approximately a quarter of animals having lesion numbers analogous to the GH parental strain. In conclusion, this study indicates that the spontaneous elastic tissue lesions observed within BN rats are consistent with an autosomal dominant, possibly single gene, effect. Moreover, epistatic effects, derived from the GH strain, may influence the severity of these lesions. The gene(s) responsible may be important in the development of conditions such as arteriosclerosis and aneurysms in humans.

Role of dietary lipids in arteriosclerosis in experimental animals.

Effects of dietary fats include the development of arteriosclerosis in humans and experimental animals, in addition to hypercholesterolemia. None of the preceding studies explicitly compared the effects of individual fatty acids. To address these issues, we chose exogenously hypercholesterolemic (ExHC) rats and apolipoprotein (apo) E deficient mice as a model for atherosclerosis and assessed the individual role of fatty acids in animals' susceptibility to atherosclerosis. The rats fed on the diet containing DHA or EPA, compared with those fed on the safflower oil (SO) diet, lowered serum cholesterol concentration, prevented platelet aggregation and slowed thickening in the ascending aorta. Apo E deficient mice developed hypercholesterolemia and severe lesion area in aortic root and arch, to a similar extent when they received DHA or SO. These results suggest a direct action of polyunsaturated fatty acids in the arterial wall, in addition to their effects on hypocholesterolemic and haemodynamic action.

Apoptosis and overexpression of bax protein and bax mRNA in smooth muscle cells within intimal hyperplasia of human radial arteries : analysis with arteriovenous fistulas used for hemodialysis.

There is a type of arteriosclerosis with remodeling of middle-size arteries in which intimal hyperplasia of smooth muscle cells (SMCs) plays the main role, and there are few macrophages, T lymphocytes, and foam cells. It is unknown whether apoptosis and the expression of Bax, an inducer of apoptosis, are increased according to the progression of this type of human arteriosclerosis, which is different from so-called atherosclerosis. Bax heterodimerizes with Bcl-2, an inhibitor of apoptosis, and the ratio of Bax to Bcl-2 determines cellular apoptosis or survival. Thus, we investigated apoptosis and the expressions of Bax, bax mRNA, and Bcl-2 in human arteriovenous (AV) fistulas used for hemodialysis, a representative of arteriosclerosis of the aforementioned type. The material was 20 radial arteries obtained from 20 patients with chronic renal failure undergoing AV shunt surgery. SMCs, macrophages, and T lymphocytes were immunohistochemically identified at the light microscopic (LM) level. Apoptosis was detected by in situ terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-dUTP nick end labeling (TUNEL) at both the LM and electron microscopic (EM) level. Cell proliferating activity was estimated by proliferating cell nuclear antigen (PCNA). Bax and Bcl-2 were detected by immunohistochemistry and Western blot analysis. Expression of bax mRNA was detected by in situ hybridization. LM TUNEL-positive cells in both the intima and media were significantly increased according to the percent stenosis of the vessels. EM analysis revealed that ultrastructures of apoptotic SMCs were seen in both synthetic and contractile phenotypes. Their frequency of occurrence in the intima and media were greater in those vessels with >50% stenosis than in those with <50% stenosis (5.2+/-0.7% versus 1.0+/-0.3% in the intima and 2. 1+/-0.5% versus 0.2+/-0.1% in the media). The proportion of apoptotic SMCs with ruptured plasma membranes was greater than that of apoptotic SMCs with intact membranes in the intima of the former (4.1+/-0.6% versus 1.1+/-0.1%). Only those SMCs with apoptotic ultrastructures had TUNEL-positive nuclei with moderate or marked accumulation of immunogold particles at the EM level. However, ultrastructures of oncosis (primary necrosis) were not observed. Immunohistochemical analyses showed significant positive correlations between percent stenosis of vessels and the percentage of either PCNA-positive intimal cells or Bax-positive areas in the intima and media. Bcl-2-positive cells were not observed in the intima but mainly in the outer media. The percentage of Bcl-2-positive medial cells was definitely decreased at an early stage after formation of the AV fistula but did not change according to the duration of hemodialysis or the progression of arteriosclerosis. Western blot analysis of Bax or Bcl-2 and in situ hybridization of bax mRNA confirmed the immunohistochemical data. Thus, regulation of cellularity in intimal hyperplasia of SMCs in human arteriosclerosis with remodeling is mediated by proliferation and apoptosis but not oncosis. The apoptosis is probably induced by an increase in the Bax to Bcl-2 ratio.

Lipoprotein(a) deposition is associated with the development of transplant renal arteriosclerosis in humans

Lipoprotein(a) deposition is associated with the development of transplant renal arteriosclerosis in humans

Potentiation of the age-dependent Ca uptake into coronary arteries of rats by the risk factor genetic hypertension.

The relationship between arterial calcification and the loss of elasticity and contractility in biological ageing is well established (1–3). Moreover, a progressive mural calcium (Ca) incorporation appears to be an underdying feature of most arteriosclerotic processes known to produce finally mural stiffness and to threaten tissue O2 supply. Interestingly, in various types of experimental and human arteriosclerosis, an initial increase in the mural Ca uptake may already characterize the early lesions (4; 5). It was the aim of the present investigations to study in rats the influences of age and genetic hypertension — an important risk factor of arteriosclerosis — on the Ca incorporation into coronary arteries.

Arteriosclerosis: its morphology in the past and today.

In a brief historical review the contributions of Rokitansky, Virchow, and Langhans concerning the pathogenesis of arteriosclerosis and the histogenetic puzzle of intimal cells classification are described. Then, some unresolved problems are discussed, especially the localization and distribution of arteriosclerotic plaques, the shape of endothelial cells and the orientation of their nuclei in correlation to local hemodynamic stress under normal and pathologic conditions. Some differences between experimental arteriosclerosis and arteriosclerosis in humans are illustrated by examples. The key role of the endothelium in the development of arteriosclerosis is well founded. According to recent investigations some cells on the surface of human arteriosclerotic plaques appear to be of non-endothelial origin. Arteriosclerosis seems to be a systemic disorder with multiorgan involvement. Individual cases, however, show significant differences in the distribution and extent of lesions. Today, arteriosclerotic research is focused on arteries being most important in clinical investigations. Nevertheless, there are also other arteries with severe arteriosclerotic lesions; for example, the degree of arteriosclerosis in periprostatic arteries is more pronounced than in coronary artery branches of the same size. Finally, the importance of primary prevention of arteriosclerosis is emphasized.

Proliferation versus atrophy--the ambivalent role of smooth muscle cells in human atherosclerosis.

Most of the current concepts on morphogenesis of atherosclerosis attribute the development of atherosclerotic lesions to the combined effects of two main cellular events: 1) activation of macrophages leading to lipoprotein phagocytosis by scavenger cells, and 2) proliferation of smooth muscle cells (SMC). SMC-like cells producing collagenous fibers and extracellular matrix are particularly involved in the formation of the so-called fibrous caps surrounding the core of an atheroma composed of foam cells and fatty debris. The fiber-forming SMC, in general, are said to result from a proliferation of media SMC which once have moved into the intima. This view of origin of the fiber-forming SMC and the alleged proliferation of media SMC is mainly derived from experimental assays exposing the vessel wall to various kinds of physical or chemical injuries. It is the purpose of this paper to demonstrate that the results of those more or less ephemeral experiments differ from findings obtained from a combined histochemical and morphometric analysis of SMC in the aortic media in spontaneous human arteriosclerosis. Instead of any proliferation, a significant atrophy of SMC occurs in the media with advancing age and progress of atherosclerosis. To some extent, this decrease in numerical and volumetric density of SMC is accompanied with intra- and extracellular calcification. It seems likely that the loss of contractile capacity of the media resulting from wasting of SMC, does slow down the stream of the interstitial fluid in the arterial wall. This stagnation must increase the life span of LDL moving through the interstitial space. The chemical alteration ensuing from aging of LDL mediates its binding to the scavenger receptors and uptake by macrophages. So far, muscular atrophy of the media forms an atherogenic factor of its own, leading to final results similar to those as known from conditions of intravascular aging of LDL in hyperlipoproteinaemia. The augmentation of SMC-like cells in the intima is hardly to be derived from the atrophic media, but rather seems to be due to local proliferation of cells which, in the normal state, do occur in small numbers in the subendothelial space. These so-called myointimal or Langhans-cells share with SMC their content of alpha-actin, but they differ by their stellate configuration from the bipolar shape SMC of the media.

Does methylmercury intoxication induce arteriosclerosis in humans? A pathological investigation of 22 autopsy cases in Niigata, Japan.

In order to clarify whether or not arterio- and/or arteriolosclerosis is induced or exacerbated in patients with methylmercury (Me-Hg) intoxication, the pathological features of arteries and arterioles in specific areas in 22 patients and 36 control subjects were examined qualitatively and quantitatively. Vessels investigated were: (1) small arteries and arterioles in the subarachnoid space and cortex of the postcentral gyrus, transverse temporal gyrus, first visual area and cerebellar vermis, as well as the myocardium and renal cortex; (2) the lateral striate artery; (3) the internal carotid, anterior, middle and posterior cerebral, basilar and vertebral arteries, as well as the coronary and renal arteries; and (4) the aorta. The arteriosclerotic changes observed in the patients with Me-Hg intoxication were indistinguishable both qualitatively and quantitatively from those of controls. The results indicate that Me-Hg intoxication does not induce or exacerbate sclerotic changes in arteries and arterioles. Thus, the peculiar neurological symptoms and neuropathological features of Me-Hg intoxication are thought to be induced not by ischemia but by selective primary degeneration of the neurons in specific regions.