Matrix metalloproteinases (MMPs) are involved in the remodeling of extracellular matrix in various tissues. Their functioning could be related to the formation of complexes, containing MMP9, MMP2, tissue inhibitor of metalloproteinases type 1 (TIMP1), and neutrophil gelatinase-associated lipocalin (NGAL). Such complexes have not been investigated in either myocardial or skeletal muscles. We examined 20 male pigs with heart failure (HF), and 5 sham-operated animals. There were no differences in the mRNA expression of MMP9, MMP2, TIMP1, and NGAL between diseased and healthy animals, in either left ventricle (LV) myocardium or skeletal muscles. In LV from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we demonstrated the presence of high molecular weight (HMW) complexes (130, 170, and 220 kDa) containing MMP9, TIMP1, and NGAL (also MMP2 in 220 kDa complex) without proteolytic activity, and a proteolytically active 115 kDa MMP9 form together with 72 and 68 kDa bands (proMMP2 and MMP2). Proteolytically active bands were also spontaneously released from HMW complexes. In skeletal muscles from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we found no HMW complexes, and proteolytic activity was associated with the presence of 72 and 68 kDa bands (proMMP2 and MMP2).
Despite advances in the management of iron deficiency in heart failure (HF), the mechanisms underlying the effects of treatment remain to be established. Iron distribution and metabolism in HF pathogenesis need to be clarified. We used a porcine tachycardia-induced cardiomyopathy model to find out how HF development influences hepatic and myocardial iron storing, focusing on ferritin, the main iron storage protein. We found that cumulative liver congestion (due to the decrease of heart function) overwhelms its capacity to recycle iron from erythrocytes. As a consequence, iron is trapped in the liver as poorly mobilized hemosiderin. What is more, the ferritin-bound Fe3+ (reflecting bioavailable iron stores), and assembled ferritin (reflecting ability to store iron) are decreased in HF progression in the liver. We demonstrate that while HF pigs show iron deficiency indices, erythropoiesis is enhanced. Renin–angiotensin–aldosterone system activation and hepatic hepcidin suppression might indicate stress erythropoiesisinduced in HF. Furthermore, assembled ferritin increases but ferritin-bound Fe3+ is reduced in myocardium, indicating that a failing heart increases the iron storage reserve but iron deficiency leads to a drop in myocardial iron stores. Together, HF in pigs leads to down-regulated iron bioavailability and reduced hepatic iron storage making iron unavailable for systemic/cardiac needs.
Adrenoceptors mediate the action of the sympathetic nervous system, including the contraction of the epididymis and vas deferens. The aim of this study was to immunolocalize the adrenergic receptors in the reproductive tract of the male cat, as this information is not yet available. The epididymis and vas deferens of domestic cats and rats (the biological controls) were analyzed by immunohistochemistry to determine the localization of the α1A-, α1B-, α1D-, α2A-, α2B-, α2C-, β1-, β2-, and β3-adrenoceptors. All the receptors were expressed in the peritubular smooth muscles of the cat, but the α1D-, α2C-, and β1-adrenoceptors were not detected in this tissue in the rat. For the α2A-adrenoceptor, the intensity of immunostaining differed significantly between the caput epididymis (weakest staining) and the vas deferens (strongest staining). The presence of all the types of the receptors was also detected in the cytoplasm of the epithelial cells in all the regions of the reproductive tract. The strong expression of the α2A-adrenoreceptor suggests it has a leading role in the contraction of the reproductive tract in the cat. The presence of other adrenergic receptors in the smooth muscle of the epididymis and vas deferens indicates a potential clinical application for α1-mimetics in the optimization of pharmacological semen collection in felids.
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