Smooth Muscle Hypertrophy Following Partial Bladder Outlet Obstruction Is Associated with Overexpression of Non-Muscle Caldesmon

• Published in: The American journal of pathology Vol. 164; no. 2; pp. 601 - 612
• Main Authors: Zhang, Erik Y., Stein, Raimund, Chang, Shaohua, Zheng, Yongmu, Zderic, Stephen A., Wein, Alan J., Chacko, Samuel
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01-02-2004; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Biomarkers; Blotting, Western; Calmodulin-Binding Proteins - biosynthesis; Hypertrophy - metabolism; Hypertrophy - pathology; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Muscle, Smooth - metabolism; Muscle, Smooth - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rabbits; Regular; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation; Urinary Bladder - pathology; Urinary Bladder - physiology; Urinary Bladder Neck Obstruction - metabolism; Urinary Bladder Neck Obstruction - pathology; Urodynamics; Anatomic pathology; Association; Urinary system; Partial; Urinary bladder; Enzyme; Caldesmon kinase; Transferases; Gene overexpression; Smooth muscle; Obstruction; Hypertrophy
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63149-5

Partial bladder outlet obstruction (PBOO) induces remodeling of urinary bladder smooth muscle (detrusor). We demonstrate an increase in bladder wall mass, muscle bundle size, and a threefold increase in the cross-sectional area of detrusor myocytes following PBOO in male New Zealand White rabbits compared to that of controls. Some bladders with detrusor hypertrophy function close to normal (compensated), whereas others were dysfunctional (decompensated), showing high intravesical pressure, large residual urine volume, and voiding difficulty. We analyzed the expression of smooth muscle-specific caldesmon (
h
-CaD) and non-muscle (
l-
CaD) by Western blotting, RT-PCR, and real-time PCR. The expression of
l
-CaD is increased significantly at the mRNA and protein levels in the decompensated bladders compared to that of normal and compensated bladders. The CaD was also co-localized with myosin containing cytoplasmic fibrils in cells dissociated from obstructed bladders and cultured overnight. Our data show that the inability of decompensated bladders to empty, despite detrusor hypertrophy, is associated with an overexpression of
l
-CaD. The level of
l-
CaD overexpression might be a useful marker to estimate the degree of detrusor remodeling and contractile dysfunction in PBOO.