Platelet-derived growth factor (PDGF) and PDGF receptors in rat corpus cavernosum: changes in expression after transient in vivo hypoxia

Abstract

Platelet-derived growth factor (PDGF) overactivity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension (hypoxia) is a known stimulus for transcriptional induction of PDGF ligand and receptor genes in different tissues. We studied the expression and localization of PDGF-A, PDGF-B, and PDGF receptor (PDGFR)-and -subunits in adult rat isolated corpus cavernosum (CC) under generalized transient hypoxia (pO 2 10%) in comparison with normoxic conditions. Semi-quantitative RT-PCR analysis of mRNA extracted from rat penis showed higher amounts of PDGF-A, PDGF-B and PDGFR-mRNA transcripts in hypoxic versus normoxic animals. The immunohistochemical analysis showed that the localization of PDGF subunits and PDGFR-was confined to the cytoplasm of the perivascular smooth muscle cells, endothelium and trabecular fibroblasts. Our findings indicate that transient low oxygen tension induces PDGF overexpression in rat CC, which in the long term may lead to an increase of connective tissue production. We suggest that a local impairment of the PDGF/PDGFR system may contribute to CC fibrosis, which is an established cause of erectile dysfunction in man.

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

“…66 In addition, NOS3 has been shown to be the most significantly increased NOS-related component in cells following chronic hypoxic insult and plays an important role in protection against future ischemic insults. 67 PDGF 49 and EPO 48 signaling have each been found to share similar protective properties against chronic hypoxia and ischemia. Thus, the increased expression of these markers may act in a neuroprotective manner and serve as an adaptation to a chronic/intermittent imbalance between oxygen supply and demand in schizophrenia.…”

“…47 Erythropoietin receptors (EPOR) are expressed in CNS neurons and have been shown to protect primary neuronal cultures against hypoxia-induced oxidative stress. 48 Transient hypoxia is also linked to increased platelet-derived growth factor (PDGF) signaling, 49 which has also been shown to reduce oxidative stress-related effects. 50 Both EPOR and PDGF receptor-b (PDGFRb) transcripts were significantly increased in schizophrenia brains.…”

“…48,49,51 Finally, if hypoxia and ETC-born ROS are prominent within cells, then oxidative damage to proteins, metabolites and DNA could result in inactive proteins, metabolites and potential DNA damage. We found protein catabolism and peptidolysis pathways to be significantly upregulated, conceivably as a result of increased protein damage (Figure 2b).…”

Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study

“…18 The reduction or absence of nocturnal erectile episodes has been reported as a possible mechanism in the pathogenesis of ED. 34 The consequent reduction in the environmental oxygen tension to which cells are exposed leads to physiological and, eventually, pathological consequences associated with differential expression of specific genes that encode for cytokines and growth factors thought to play key roles in the regulation of synthesis and assembly of connective tissue proteins, that is, transforming growth factor-b1 and pltelet-derived growth factor, 35 which are overexpressed in tunica albuginea from men suffering from venocclusive dysfunction 36 and in plaques obtained from Peyronie's disease. 37 Reports on the improvement of morning erections after short-acting PDE5i assumption is frequent if the drug is taken daily at bedtime 38 but this effect is lost after 2 or 3 days of withdrawal.…”

Is there an association of allergy and cardiovascular disease?

“…The se substan ces are in vol ved in vas cu lar myo cytes hyperpla sia and in crea sed pro duc tion of extra cel lu lar mat rix, con tai ni ng col la gen type I and III, elas tin, pro teog lyca ns (8). In fl am ma to ry-pro li fe ra ti ve changes in the en dot he lium and the in ti ma lead to patho lo gic ves sel wa ll re mo de li ng and plaque for mation.…”