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Figure 6 Mean CYR61 gene expression in the transitional zone of the prostate taken from normal controls, patients with asymptomatic benign prostatic hyperplasia (BPH) (A), symptomatic BPH (B), and BPH with prostate cancer (C): *P<0.05; **P<0.005; ***P<0.001 versus normal controls. (Reproduced with kind permission from Sakamoto, S.; Yokoyama, M.; Zhang, X.; Prakash, K.; Nagao, K.; Hatanaka, T.; Getzenberg, R. H.; Kakehi, Y. Endocrinology 2004, 145, 2929-2940, copyright © 2004 The Endocrine Society.)

as IL1b, which results in more growth, more demand on oxygen and increased production of growth factors. An upregulation of hypoxia inducible factor-1 (HIF-1) is thought to be the key mediator responsible for excess production of these growth factors. It is possible that HIF-1 is a prostate' response to excessive cell proliferation, i.e., the promotion of a hypoxic state, which is likely to destroy cells by starving them of oxygen, may re-address the loss of apoptosis in BPH tissue. Alternatively, the prostate may be fooled into thinking that it is dying and HIF-1 could be increased as a way of promoting growth. A number of other growth-promoting factors have also been shown to increase during the development of BPH, including activated protein kinases and VEGF17 In addition, polyamines are important stimulators of proliferation, and it has been suggested that an increase in facilitators of the polyamine-biosynthesis pathway (such as ornithine decarboxylase) could be responsible for the resultant increase in cell growth.18 With regard to apoptosis, there is evidence to suggest that abnormal expression of apoptotic regulators and growth suppression factors, such as Bcl-2, BAX and p27/Kip1, may be the trigger for reduced apoptosis in hyperplastic cells.19 Cells in BPH tissue can also lose their ability to proliferate or undergo apoptosis, these cells remain in a metabolically active state and can even accumulate; this process is known as senescence. Senescent cells are a common feature of aging tissue, and can be caused by deoxyribonucleic acid (DNA) damage, oxidative stress, and inappropriate expression of oncogenes. Senescent cells are highly prevalent in BPH tissue, particularly in the epithelium, and a key senescence biomarker known as senescence-associated b-galactosidase (SA-b-gal) has been found to be present in more than 80% of BPH tissues from large prostates, i.e., those with a weight greater than 55 g.20 These cells can have altered function, characterized by increased expression of cytokines, growth factors and PTHrP, and reduced expression of protease inhibitors; and they may have an active role in the development of BPH as they drive the proliferation of neighboring nonsenescent cells. SA-b-gal strongly correlates with IL1a and IL8 production, leading researchers to suggest that ILs are actively involved in the development of senescence. IL8 also correlates with prostate weight. As senescence is thought to be a proliferation-limiting factor, it follows that prostate volume may be a trigger for increased production of ILs as a way of preventing further growth; however, the impact of senescent cells on their neighboring nonsenescent cells does not fit neatly into this theory.

6.24.3.4 Remodeling

Remodeling has recently been proposed as a model of BPH development and progression. It is characterized by hypertrophic basal cells, calcification, clogged ducts, inflammation and elevated proinflammatory markers, increased reactive oxygen species (ROS), and TGFb1.21 There is evidence to suggest that an increase in TGFb1, which is possibly due to increased secretion from proliferating or senescent cells, converts fibroblasts into 'reactive'

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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