Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The atherosclerotic intimal lesion contains endothelial cells, smooth muscle cells, monocytes/macrophages and T lymphocytes, which constitute a histamine-cytokine network that participates in chronic inflammatory responses. Monocytes/macrophages and T lymphocytes express the histamine-producing enzyme histidine decarboxylase (HDC), and specific histamine receptors (HHR), which are switched from HH2R to HHR1 during macrophage differentiation. Endothelial and smooth muscle cells also express HHR in response to histamine. The effects of histamine on these cells include a regulation of atherosclerosis-related events such as cell proliferation, expression of matrix metalloproteinase, adhesion molecules and cytokines. Furthermore, recent studies have indicated that histamine and the activation of its specific receptors modulate the Th1/Th2 balance in inflammatory lesions through the regulation of cytokine production from inflammatory cells. The histamine-cytokine network in the atherosclerotic intima could regulate inflammatory and immune responses, including Th1/Th2 balance, and contribute to atherogenesis.
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PMID:Role of macrophage-derived histamine in atherosclerosis-- chronic participation in the inflammatory response --. 1525 63

To clarify the role of histamine-producing cells and its origin in atherosclerosis, we investigated histidine decarboxylase (HDC; histamine-producing enzyme) expression in murine arteries with vascular injuries after the animal had received transplanted bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. The neointima in the ligated carotid arteries contained BM-derived HDC+ cells that expressed macrophage (Mac-3) or smooth muscle cell antigen (alpha-SMA). In contrast, the HDC+ BM-derived cells, which were positive for Mac-3, were mainly located in the adventitia in the cuff replacement model. In apolipoprotein E-knockout mice on a high cholesterol diet, BM-derived cells expressing Mac-3 in the atheromatous plaques were also positive for HDC. In comparison with wild-type mice, HDC-/- mice showed reduced neointimal thickening and a decreased intima-to-media ratio after ligation and cuff replacement. These results indicate that histamine produced from BM-derived progenitor cells, which could transdifferentiate into SMC- or macrophage-like cells, are important for the formation of neointima and atheromatous plaques.
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PMID:Role of histamine produced by bone marrow-derived vascular cells in pathogenesis of atherosclerosis. 1583 15

Since its discovery in 1910, histamine has been regarded as one of the most important biogenic amines in the medical and biological fields. This article summarizes the information about the role of histamine in allergic situations, atherosclerosis, and autoimmune encephalomyelitis, especially focusing on our study with histidine decarboxylase gene knockout mouse. In the allergic bronchial asthma model, histamine positively controls eosinophilia but not bronchial hypersensitivity. Histamine is proved to be an important substance that controls body temperature and respiration in systemic anaphylaxis but its role in controlling blood pressure is minor. Histamine also plays a role in inducing atherosclerosis in the mouse model. We showed that experimental autoimmune encephalomyelitis (EAE) is significantly more severe in histamine-deficient mice with diffuse inflammatory infiltrates in the brain and cerebellum, including a prevalent granulocytic component. Histamine is mainly produced in mast cells and basophils in hematopoietic cells. We've shown that mast cells not only produce histamine, but also uptake it from the environmental medium and release it by allergic stimulants. The protein used for the plasma transport of histamine in basophils was identified as organic cation transporter (OCT3).
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PMID:Progress in allergy signal research on mast cells: the role of histamine in immunological and cardiovascular disease and the transporting system of histamine in the cell. 1836 91

Given the very difficult odyssey of my early years, who could have imagined the incredible and successful journey that constituted my life path after age 13? I was born into a Jewish family in Breslau, Germany, right before the rise of Nazism and Hitler's election. After Kristallnacht, when my father was taken to Buchenwald Concentration Camp, we had to leave Germany as soon as possible. The first opportunity came in May of 1939, when we boarded the SS St. Louis bound for Havana, Cuba. Almost all passengers were denied entrance into Cuba, and the ship had to go back to Europe, where I ended up in France. In December of 1939, during World War II, I was fortunate to be able to leave France. This time I made it to Cuba, where my father was already in residence. A year later, my entire family was allowed into the United States. I took advantage of all the educational resources in this land of opportunity. I graduated valedictorian of my high school class and earned a four-year scholarship to Rutgers University, where I obtained a Bachelor of Science degree. I went on to earn a Master's degree from the University of Connecticut and finally a PhD from the University of Illinois. Within two months after graduating from Illinois, I was hired as an assistant professor of nutritional biochemistry at Rutgers, where I enjoyed a most productive research and teaching career. My PhD research involved tryptophan and niacin metabolism in the chick, and upon arrival at Rutgers I continued amino acid studies with the goal of assessing the essential amino acid requirements for egg production. This research was crowned with success and was followed with amino acid requirement studies for maintenance and for growth in rabbits, and ultimately with a reevaluation of requirements in adult humans. An outgrowth of the maintenance requirements led to a series of investigations into the metabolism of histidine, histamine, and carnosine (a histidine-containing dipeptide). Histamine, we found, plays an important role in wound healing and stress management. Pyridoxal phosphate is the cofactor for the enzyme histidine decarboxylase required for histamine synthesis and similarly serves as a cofactor for hydroxytryptophan decarboxylase, the enzyme that is part of the pathway to serotonin synthesis. Investigations into these pathways led to interesting findings: brain concentrations of serotonin could be increased by supplementing the diet of rats with tryptophan and pyridoxine; the elevated brain serotonin levels had behavioral consequences. Alcohol craving, addiction, and withdrawal symptoms are affected by serotonin concentrations in the brain, and alleviation of these conditions can be achieved with simultaneous administration of serotonin and dopamine agonists. In the midst of our early amino acid studies, we serendipitously also became involved with lipid metabolism in relation to atherosclerosis and blood cholesterol in a chicken model. This work led to the recognition that soluble fibers, like pectin, had strong cholesterol-lowering properties that were beneficial in lowering the incidence of coronary plaque formation. The research success that I have enjoyed has been coupled with the gift of three accomplished children who are making important contributions as professionals in their fields of endeavor. My wife and I are also blessed with 10 wonderful grandchildren, our pride and joy!
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PMID:From tryptophan to hydroxytryptophan: reflections on a busy life. 1940 Jul 2

Histamine, a classic low-molecular-weight amine, is synthesized from L-histidine by histidine decarboxylase (HDC), and histamine-specific receptors (HRs) are essential for its actions. Our serial in vivo studies have uniquely reported that expression of histamine/HRs is variably identified in atherosclerotic lesions, and that HDC-gene knockout mice without histamine/HRs signaling show a marked reduction of atherosclerotic progression. These data have convinced us that histamine plays a pivotal role in the pathogenesis of atherosclerosis. Among four subclasses of HRs, the expression profile of the main receptors (H1/2R) has been shown to be switched from H2R to H1R during monocyte to macrophage differentiation, and H1R is also predominant in smooth muscle and endothelial cells of atheromatous plaque. Using various animal models of H1/2R-gene knockout mice, H1R and H2R were found to reciprocally but critically regulate not only hypercholesterolemia-induced atherosclerosis and injury-induced arteriosclerosis, but also hyperlipidemia-induced nonalcoholic fatty liver disease (NAFLD). Metabolic syndrome manifests obesity, dyslipidemia, insulin resistance, atherosclerosis, and/or NAFLD, i.e. the dysregulation of lipid/bile acid/glucose metabolism. Therefore, although its etiology is complicated and multifactorial, histamine/HRs signaling has a close relationship with the development of metabolic syndrome. We herein review diverse, key in vivo roles of histamine/HR signaling in the pathogenesis of metabolic syndrome.
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PMID:Critical in vivo roles of histamine and histamine receptor signaling in animal models of metabolic syndrome. 2786 77

Kounis syndrome (KS) is a complex of cardiovascular symptoms and signs following either allergy or hypersensitivity and anaphylactic or anaphylactoid insults. We report the case of 57-year-old man, with hypertension and history of allergy, referred for facial rash and palpitations appeared after consumption of canned tuna fish. Suddenly, the patient collapsed: electrocardiogram showed ST-elevation in inferior leads. The patient was transferred from the spoke emergency room for coronary angio, which did not show any sign of coronary atherosclerosis. A transient coronary spasm was therefore hypothesized and the final diagnosis was KS. To the best of our knowledge, this is one of the first cases of KS following the ingestion of tuna fish. KS secondary to food allergy has also been reported, and shellfish ingestion has been considered as one of the most active KS inducer foods. Canned tuna fish too is well known as an allergy inducer. Tuna fish allergy should be considered, however, within the context of scombroid food poisoning, also called histamine fish poisoning. Fish with high levels of free histidine, the enzyme substrate converted to histamine by bacterial histidine decarboxylase, are those most often implicated in scombroid poisoning. Inflammatory mediators such as histamine constitute the pathophysiologic basis of Kounis hypersensitivity-associated acute coronary syndrome. Patients with coronary risk factors, allergic reaction after food ingestion, and suspected scombroid poisoning should be therefore carefully monitored for a prompt diagnosis of possible coronary complications.
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PMID:Kounis syndrome following canned tuna fish ingestion. 2801 91


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