Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.

• MeSH
• biologické modely MeSH
• endoglin genetika   metabolismus   MeSH
• endoteliální buňky metabolismus   MeSH
• exprese genu MeSH
• faktor stimulující granulocyto-makrofágové kolonie metabolismus   MeSH
• faktor stimulující kolonie makrofágů metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• matrixová metaloproteinasa 12 metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• zánět etiologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bronchiální astma * farmakoterapie   MeSH
• lidé MeSH
• matrixová metaloproteinasa 12 * MeSH
• myši MeSH
• plíce MeSH
• sloučeniny síry MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The project was scheduled as a case-control study to investigate the correlation between MMP-2 (rs243864), MMP-9 (3918242), MMP-12 (rs7123600) and TIMP-2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP-2 genotypes and phenotypes of CVD. MATERIAL AND METHODS: 150 patients with CVD and 227 controls were enrolled into the study. The MMPs and TIMP-2 genotypes were identified by the PCR method and restriction analysis according to standard protocols. RESULTS: The G allele of MMP-2 -790 T/G was 1.85 times more frequent in men with CVD than in the control group (P = 0.008). The T allele of MMP-9 -1562 C/T was observed 2.571 times more frequently in patients with CVD than in the control individuals (both in men and women) with clinically significant specificity (P = 0.0000009). The G allele of MMP-12 rs7123600 was determined 2.082 times more frequently in female patients with CVD than in the control group with clinically significant specificity (P = 0.02). No significant result in TIMP-2 rs8176329 polymorphism in the case-control study was observed. CVD women with G allele in MMP-2 -790 T/G in the genotype-phenotype study are seen to develop ulceration 2.539 times more frequently (P = 0.003). The G allele of MMP-12 rs7123600 was detected 3.167 times more frequently in CVD women with ulceration compared with CVD women without ulceration (P = 0.007). In CVD men in C6 stage, the incidence of AG genotype in rs7123600 MMP-12 polymorphism was found to be 4.675 times higher compared to CVD women with C6 staging (P = 0.005). The AG genotype in TIMP 2 rs8176329 polymorphism was found to be associated with higher risk of tumour (P = 0.01). CONCLUSION: Studying these polymorphisms can contribute to better identification of patients at higher risk of developing CVD, while providing the most appropriate prevention and treatment strategies for limiting the progression and complications of CVD.

• MeSH
• chronická nemoc MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixové metaloproteinasy genetika   MeSH
• mladý dospělý MeSH
• polymerázová řetězová reakce MeSH
• progrese nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tkáňový inhibitor metaloproteinasy 2 genetika   MeSH
• žilní insuficience komplikace   genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

PURPOSE OF REVIEW: Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019. RECENT FINDINGS: In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce. SUMMARY: Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.

• MeSH
• biologické markery metabolismus   MeSH
• bronchiální astma farmakoterapie   enzymologie   etiologie   patofyziologie   MeSH
• chronická obstrukční plicní nemoc farmakoterapie   enzymologie   etiologie   patofyziologie   MeSH
• COVID-19 enzymologie   etiologie   patofyziologie   MeSH
• farmakoterapie COVID-19 MeSH
• idiopatická plicní fibróza farmakoterapie   enzymologie   etiologie   patofyziologie   MeSH
• inhibitory matrixových metaloproteinas terapeutické užití   MeSH
• lidé MeSH
• matrixová metaloproteinasa 12 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• antiinfekční látky lokální * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• chlorhexidin škodlivé účinky   terapeutické užití   MeSH
• chronická nemoc MeSH
• endotoxiny škodlivé účinky   MeSH
• exotoxiny škodlivé účinky   MeSH
• hexany terapeutické užití   MeSH
• hojení ran * imunologie   účinky léků   MeSH
• infekce měkkých tkání komplikace   prevence a kontrola   terapie   MeSH
• infekce v ráně * farmakoterapie   komplikace   prevence a kontrola   MeSH
• jod terapeutické užití   MeSH
• lidé MeSH
• matrixová metaloproteinasa 12 škodlivé účinky   MeSH
• med MeSH
• stříbro terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• adjuvantní chemoterapie MeSH
• inhibitory matrixových metaloproteinas MeSH
• kombinovaná terapie MeSH
• malobuněčný karcinom plic farmakoterapie   terapie   MeSH
• matrixová metaloproteinasa 12 MeSH
• nádory jícnu epidemiologie   chirurgie   terapie   MeSH
• nádory plic diagnóza   MeSH
• nemalobuněčný karcinom plic farmakoterapie   terapie   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• vnitřní lékařství

Multiple sclerosis is a chronic demyelinating disease of the central nervous system in which the genetic background plays an important role. Its pathophysiology is characterised by two major processes: neuroinflammation and neurodegeneration. Matrix metalloproteinases are involved in both of them. Macrophage metalloelastase is one of the three matrix metalloproteinases the common elevation of which has been confirmed in multiple sclerosis and also in animal models with experimental allergic encephalomyelitis. To assess the association between its promotor polymorphism and demyelinating disease we genotyped a total of 92 patients (23 men, 69 women, mean age 37 years) with definite multiple sclerosis (according to the McDonald criteria) and 51 healthy controls (17 men, 34 women) matched for age and sex. Genotyping was performed by means of polymerase chain reaction with restriction analysis. We observed no statistically significant differences in genotype or allele distribution of –82 A/G polymorphism between the groups examined (OR=2.6, p=0.026, pcorr=0.078). Due to insufficient numbers of patients with the progressive form [9], no statistically significant differences in genotype or allele frequencies emerged among the patients with variant forms of multiple sclerosis. Nevertheless, all patients with the progressive form (which is associated with a more severe course and higher disability) were of the same genotype: homozygotes AA. This genotype is connected with higher promotor activity and a higher expression of the final protein. It may represent a variant genotype base for a different course of multiple sclerosis in the polymorphism under investigation.

• MeSH
• financování organizované MeSH
• genetické techniky využití   MeSH
• genetický výzkum MeSH
• genotyp MeSH
• lidé MeSH
• matrixová metaloproteinasa 12 genetika   MeSH
• polymerázová řetězová reakce metody   využití   MeSH
• polymorfismus genetický genetika   MeSH
• roztroušená skleróza etiologie   genetika   MeSH
• statistika jako téma metody   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH

Caspase-12 is a molecule whose functions are still not well understood. Although its expression has been found in various tissues, specific roles have been described in only a few cases. These include the effect of caspase-12 on murine bone cell differentiation during craniofacial development. This work focused on the development of the limbs taking place through endochondral ossification, which precedes the formation of the cartilaginous growth plate. Caspase-12 was described here for the first time in growth plate chondrocytes during physiological development. Using pharmacological inhibition, caspase-12 was found to affect chondrogenesis. Limb-derived micromass cultures showed a significantly increased area of chondrogenic nodules after caspase-12 inhibition and there were changes in gene expression, the most significant of which was the reduction of Mmp9. These data point to potential new functions of caspase-12 in chondrogenesis.

• MeSH
• buněčná diferenciace MeSH
• chondrocyty * MeSH
• chondrogeneze * fyziologie   MeSH
• inhibitory kaspas farmakologie   MeSH
• kaspasa 12 * metabolismus   genetika   MeSH
• kultivované buňky MeSH
• matrixová metaloproteinasa 9 metabolismus   genetika   MeSH
• myši MeSH
• růstová ploténka růst a vývoj   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Assesment of genetic variability of MMP, TIMP and ACE genes in respect to acute infarct myocardum and its intermediate phenotype, inclusive of the analysis of selected serum levels. For detection of pholymorphisms in promoter and intone regions, PCR andRFLP methods will be used. New polymorphisms in regulatory regions of MMP and TIMP genes will be detected by heteroduplex analysis and SSCP. The serum levels will be measured by ELISA method. The "case-control" (association) study will be used to assessthe relation between genotype and disease. The data will be summarised by common statistic methods (chi-square test, Fisher's exact test and odds ratio) and further the analysis of risk factors is planed.

Zhodnocení genetické variability genů pro MMP, TIMP a ACE vzhledem k akutnímu infarktu myokardu a jeho intermediálnímu fenotypu, včetně analýzy sérovýchh hladin vybraných působků. Metod PCR a RFLP bude využito ke stanovení promotorových a intronových polymorfismů. Nové polymorfismy budou v regulačních oblastech genů detekovány pomocí heteroduplexní analýzy a SSCP. Proteinové hladiny vybraných působků budou hodnoceny pomocí ELISA metody. K vyjádření vtahu mezi genotypy a onemocněním bude využita tzv. "case-control" studie (asociační studie - "případ-kontroly"). Data budou sumarizována jednak běžnými statickým metodami (chi-kvadrát test, Fisher exakt test, odds ratio, ..) zaměřenými na hlavní cílové parametry projektu a dále je plánována vícerozměrná analýza rizikových faktorů.

• MeSH
• beta blokátory terapeutické užití   MeSH
• infarkt myokardu MeSH
• inhibitory ACE terapeutické užití   MeSH
• inhibitory matrixových metaloproteinas MeSH
• matrixová metaloproteinasa 12 MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus genetický MeSH
• polymorfismus konformace jednovláknové DNA MeSH
• prognóza MeSH
• remodelace komor MeSH
• tkáňové inhibitory metaloproteinas MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• kardiologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR