Pulmonary hypertension is a complex and heterogeneous condition with five main subtypes (groups). This review focuses on pulmonary hypertension caused by chronic hypoxia (hypoxic pulmonary hypertension, HPH, group 3). It is based mainly on our own experimental work, especially our collaboration with the group of Professor Herget, whose fifth anniversary of death we commemorate. We have found that oxidation and degradation of the extracellular matrix (ECM) in vitro, in either the presence or the absence of pro-inflammatory cells, activate vascular smooth muscle cell (VSMC) proliferation. Significant changes in the ECM of pulmonary arteries also occurred in vivo in hypoxic rats, namely a decrease in collagen VI and an increase in matrix metalloproteinase 9 (MMP-9) in the tunica media, which may also contribute to the growth activation of VSMCs. The proliferation of VSMCs was also enhanced in their co-culture with macrophages, most likely due to the paracrine production of growth factors in these cells. However, hypoxia itself has a dual effect: on the one hand, it can activate VSMC proliferation and hyperplasia, but on the other hand, it can also induce VSMC hypertrophy and increased expression of contractile markers in these cells. The influence of hypoxia-inducible factors, microRNAs and galectin-3 in the initiation and development of HPH, and the role of cell types other than VSMCs (endothelial cells, adventitial fibroblasts) are also discussed. Keywords: Vasoconstriction, Remodeling, Oxidation, Degradation, Extracellular matrix, Collagen, Proteolytic enzymes, Metalloproteinases, Macrophages, Mast cells, Smooth muscle cells, Endothelial cells, Fibroblasts, Mesenchymal stem cells, Hypoxia-inducible factor, microRNA, Galectins, Hyperplasia, Hypertrophy, Therapy of hypoxic pulmonary hypertension.

• MeSH
• hypoxie * metabolismus   MeSH
• lidé MeSH
• myocyty hladké svaloviny * metabolismus   patologie   MeSH
• plicní hypertenze * metabolismus   patologie   MeSH
• proliferace buněk MeSH
• svaly hladké cévní * metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS.

• MeSH
• fluorescenční mikroskopie MeSH
• glykosylace MeSH
• kyselina peroxydusitá metabolismus   MeSH
• lysin analogy a deriváty   metabolismus   MeSH
• mozek růst a vývoj   metabolismus   MeSH
• novorozená zvířata MeSH
• oxidační stres * MeSH
• peroxid vodíku metabolismus   MeSH
• peroxidace lipidů MeSH
• posttranslační úpravy proteinů MeSH
• potkani Wistar MeSH
• reaktivní formy dusíku metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• superoxidy metabolismus   MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3-nitrotyrosine MeSH Prohlížeč
• kyselina peroxydusitá MeSH
• lysin MeSH
• N(6)-carboxyethyllysine MeSH Prohlížeč
• peroxid vodíku MeSH
• reaktivní formy dusíku MeSH
• reaktivní formy kyslíku MeSH
• superoxidy MeSH
• tyrosin MeSH

Reports describing production of reactive oxygen species in neonatal heart are missing. As lysyl oxidase is potentially important source of H(2)O(2), we studied its role during ontogenic development of rat heart. H(2)O(2) was detected in thin sections of developing rat heart by fluorescence microscopy with the use of fluorescence probe 2'-7'-dichlorofluorescin. The experimental design comprised foetuses 21 days after conception, and then the animals sampled on the 1st, 4th, 7th, 10th, 15th, 30th and 60th day after birth. We also used 7-month-old animals as an example of ageing effects. Since the day 4 on, H(2)O(2) was produced only extracellularly up to the day 15, between days 30 and 60 intracellular production was detected as well, and in 7-month-old animals only extracellular production was observed. The specific inhibitors of lysyl oxidase almost completely quenched the H(2)O(2)-dependent fluorescence. Starting from day 7, blue autofluorescence specific to oxidized proteins developed in the vessel wall. Intracellular blue autofluorescence specific to autoxidation products developed after day 30. Chloroform extraction diminished the intracellular blue fluorescence, leaving the extracellular fluorescence intact. This confirmed the protein nature of the fluorophores. Lysyl oxidase is significant source of H(2)O(2) in the heart vessel wall during development and H(2)O(2) oxidatively modifies elastin producing protein blue autofluorescence.

• MeSH
• chloroform MeSH
• elastin metabolismus   MeSH
• fluoresceiny metabolismus   MeSH
• fluorescence MeSH
• fluorescenční barviva metabolismus   MeSH
• krysa rodu Rattus MeSH
• lysyloxidasa metabolismus   MeSH
• myokard enzymologie   metabolismus   MeSH
• oxaziny metabolismus   MeSH
• peroxid vodíku metabolismus   MeSH
• potkani Wistar MeSH
• srdce růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2',7'-dichlorofluorescein MeSH Prohlížeč
• chloroform MeSH
• elastin MeSH
• fluoresceiny MeSH
• fluorescenční barviva MeSH
• lysyloxidasa MeSH
• oxaziny MeSH
• PAcein MeSH Prohlížeč
• peroxid vodíku MeSH