Background
Methods
Results
Alterations occurring in the urothelium and suburothelium
Alterations occurring in the detrusor muscle: morphological aspects
Author, year | Study design | Subjects in the case group (n) | Main findings |
---|---|---|---|
Gosling, 1980 [15] | Case control | 9 | • ↑ intrafascicular and interfascicular collagen • ↓ SMCs diameter |
Gilpin, 1985 [10] | Case control | 14 | • ↑connective tissue infiltration of some smooth muscle bundles in 12/14 patients • ↑ SMCs mean profile area |
Elbadawi, 1993 [12] | Case control | 7 | • ↓ intermediate cell junctions • ↑intrafascicular collagen and elastic fibers • ↑ SMCs hypertrophy • ↑ SMCs and axons degeneration in patients with impaired detrusor contractility |
Inui, 1999 [19] | Case control | 26 | • Significant positive linear relationship between C/M and estimated bladder weight in patients with bladder weight ≥ 60 g • ↑ C/M in patients with bladder weight ≥ 60 g |
Tse, 2000 [13] | Case control | 9 | • Myohypertrophy pattern in all cases |
Brierly, 2003 [14] | Case control | 12 | • Myohypertrophy pattern in 8/10 BOO patients. • Degenerative pattern in 4/10 BOO patients. |
Holm, 2003 [22] | Case control | 25 | • Significant correlation between intra- and interfascicular elastin and BOO degree |
Mirone, 2004 [15] | Case control | 36 | • ↑collagen content in BPO patients with respect to controls • ↑collagen content in patients with severe symptoms |
Horn, 2004 [44] | Observational | 54 | • Correlation between abnormal morphology and impaired bladder compliance and decreased capacity |
Collado, 2006 [11] | Case control | 33 | • ↑ intrafascicular and interfascicular collagen • ↑ intrafascicular fibrosis in BOO patients with history of AUR • ↑ SMCs diameter in BOO patients with respect to controls • Not significant differences in terms of SMCs diameter between BOO patients with and without AUR history • Positive correlation between SMCs diameter and symptoms duration |
Rubinstein, 2007 [18] | Case control | 10 | • ↑ collagen and elastic fibers |
Blatt, 2012 [16] | Case control | 17 | • Poor post-TURP voiding outcome in patients with detrusor ultrastructural pattern characterized by variable muscle cell size, muscle cell shape, abnormal fascicle arrangement and collagenosis. |
Bellucci, 2017 [21] | Case control | 19 | • ↑ C/M • Significant negative correlation between C/M and bladder compliance • Significant correlation between the probability of urinary retention and C/M |
Averbeck, 2017 [20] | Observational | 38 | • ↑ C/M in patients with PVR ≥ 200 mL and in those with reduced bladder compliance |
SMCs alterations
ECM alterations
Alterations occurring in the detrusor muscle: molecular aspects and signaling pathways
Author, year | Experimental conditions | Molecular alteration | Cellular events |
---|---|---|---|
Backhaus, 2002 [34] | HBSMCs exposed to HP (0.3, 20 and 40 cm H2O) for 1, 3, 7 and 24 h | ↓ MMP-1, 2, 9 after exposure to 20 cm H2O for 7 h ↑TIMP-1 after exposure to 40 cm H2O 3, 7 and 24 h | |
Wang, 2013 [24] | HBSMCs exposed to HP (0, 20, 40, 60, 80 and 100 cm H2O) for 6, 12, 24 and 72 h | ↓expression of the gap junction connexin 43 under HP > 60 cm H2O for 24 h or HP > 40 cm H2O for 72 h. | |
Chen, 2012 [28] | HBSMCs exposed to CHP (0, 100, 200, and 300 cm H2O) | ↑ SGK1 expression and activity | ↑ proliferation in the 200 and 300 cm H2O groups |
Chen, 2014 [32] | HBSMCs exposed to CHP (0, 100, 200, and 300 cm H2O) | ↑ Skp2 expression and ↓ p27 expression under 200 and 300 cmH2O CHP | |
Wu, 2012 [31] | HBSMCs exposed to CHP (static, 100, 200, and 300 cm H2O) | Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 activated by 200 and 300 cmH2O CHP | ↑proliferation under 200 and 300 cmH2O CHP |
Preis, 2015 [27] | HBSMCs exposed to HP of 136 cm H2O for 1 h | ↑ expression of PDGFR α and β | ↑ proliferation |
Sun, 2016 [29] | HBSMCs exposed to CHP up to 200 cm H2O | ↑ miR-3180-5p | ↑ proliferation |
Sun, 2017 [30] | HBSMCs exposed to CHP up to 200 cm H2O | ↑ miR 4323 | ↑ proliferation |
Lee, 2006 [25] | HBSMCs exposed to HP (40 cm H2O) and/or acetylcholine for 24 h | Activation of muscarinic receptors | ↑ proliferation ↑ hypertrophy |
Lee, 2008 [26] | HBSMCs exposed to acetylcholine in the presence or absence of HP (10, 20, and 40 cm H2O) | ↑ M2 and M3 receptors expression | ↑ proliferation ↑ hypertrophy |
Yang, 2008 [23] | HBSMCs exposed to cyclic stretch with maximum of 15% strain magnitude at a frequency of 0.3 Hz for either 1 h or 24 h. | 30 genes upregulated and 59 downregulated after 1 h exposure 59 genes upregulated and 27 downregulated after 24 h exposure | |
Backhaus, 2002 [34] | HBSMCs exposed to HP (0.3, 20 and 40 cm H2O) | ↓ MMP-1, 2, 9 ↑TIMP-1 | |
Liang, 2017 [33] | HBSMCs exposed to HP (100, 200, or 300 cm H2O) and/or acetylcholine | ↑ IL-6, monocyte chemoattractant protein, and RANTES | |
Galvin, 2004 [7] | HBSMCs exposed to 1% O2tension for 24, 48, 72, and 96 h | ↑ HIF-1α ↑ VEGF ↑ p27kip1 | ↓ proliferation |
Wiafe, 2017 [35] | HBSMCs exposed to 3% O2tension for 2, 24, 48, and 72 h | ↑ HIF1α, HIF2α, and HIF3α ↑VEGF ↑TGFβ1 ↑CTGF ↑ collagens 1, 2, 3, 4 ↑ fibronectin ↑aggrecan ↑TIMP ↑ α-smooth muscle actin ↑vimentin, ↑desmin ↑TNFα, IL 1β, and IL 6 ↓ IL-10 | |
Boopathi , 2011 [38] | Bladder samples from subjects with BOO and controls | ↑ expression of GATA-6 in cases ↓ Caveolin-1 expression | |
Koritsiadis, 2008 [36] | Bladder samples from subjects scheduled for BPE-surgery and controls | ↑ HIF-1α expression in stromal cells between muscle bundles and in connective tissue beneath the mucosal layer | |
Barbosa, 2017 [37] | Bladder samples from subjects with obstructive BPE and controls | ↑ collagens I and III ↓ MMP-9 and TIMP-1 ↑VEGF ↓ CD105 | |
Gheinani, 2017 [43] | Bladder samples from subjects with different states of urodynamic defined BOO-induced bladder dysfunction | Progressive increase in the number of altered mRNA and miRNAs from the detrusor overactive to the obstruction group to the underactive detrusor groups |
Effects of cyclic stretch
Effects of increased pressure
Effects of increased pressure on cell adhesion
Effects of increased pressure on cell hypertrophy and hyperplasia
Effects of increased pressure on inflammatory pathways
Effects of increased pressure on ECM remodeling
Effects of hypoxia
Effects of hypoxia on hypoxia inducible factor and vascular endothelial growth factor
Effects of hypoxia on HBSMCs proliferation
Effects of hypoxia on HBSMCs differentiation
Effects of hypoxia on inflammatory pathways
Other SMCs molecular alterations
Alterations occurring in the neuronal compartment
Author, year | Study design | Subjects in the cases group (n) | Findings |
---|---|---|---|
Gosling, 1986 [39] | Case-control | 19 | ↓ autonomic nerve supply |
Chapple, 1992 [41] | Case-control | 19 | ↓ density of innervation by vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P and somatostatin immunoreactive nerve fibers in the obstructed bladder. |
Cumming, 1992 [40] | Case-control | 10 | ↓innervation |
Elbadawi, 1993 [12] | Case control | 7 | ↑axon degeneration in patients with impaired detrusor contractility |
Steers, 1991 [42] | Case-control | – | ↑ NGF in grossly hypertrophied human bladders |
Barbosa, 2017 [37] | Case-control | 43 | ↑ NGF receptor expression in smokers and dyslipidemic patients |