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From the Departments of * Urology and
Clinical Biochemistry, Medicine School of
Harran University, Sanliurfa, Turkey
| Correspondence to: Dr Murat Savas, Urology Department, Medicine School of Harran University, 63100 Sanliurfa, Turkey (e-mail: mrtsvs{at}yahoo.com). |
| Received for publication July 12, 2009; accepted for publication September 23, 2009. |
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Abstract |
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Key words: Collagen turnover, extracellular matrix, oxidative stress
Erectile dysfunction (ED) is defined as the consistent inability to obtain or maintain an erection for satisfactory sexual intercourse. Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin. Patients who had a vascular evaluation and vascular pathology can classify as arteriogenic ED, venogenic ED, and mixed vasculogenic ED (Tal et al, 2009). The incidence of ED dramatically increases in men with diabetes mellitus, hypercholesterolemia, and cardiovascular disease. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction play an integral role in the occurrence of ED in this cohort of men. ED is highly prevalent in men with cardiovascular disease, and because cardiovascular disease is well known to be associated with endothelial dysfunction, one can infer that endothelial dysfunction of the penile vascular tree may contribute to impairments in erectile function. Therefore, it has been hypothesized that endothelial dysfunction can result in ED (Maas et al, 2002; Solomon et al, 2003). Atherosclerotic plaques initially consist of fatty streaks that develop into fibroproliferative lesions. A mature lesion consists mainly of foam cells, smooth muscle cells (SMCs), a necrotic core, and a fibrous cap containing extracellular matrix components. The principal matrix proteins in plaques are type I and type III collagens, proteoglycans, and elastin, with collagens accounting for up to 60% of the total protein content (Watanabe et al, 2003). Measurement of circulating levels of extracellular matrix turnover biomarkers, such as the matrix metalloproteinases and the tissue inhibitors of metalloproteinases, has long been used in the evaluation of atherosclerosis (Myara et al, 1982; Gensini, 1983). Accordingly, we have hypothesized that the serum level of prolidase activity would increase in ED, because increased extracellular matrix turnover is a pathophysiologic mechanism in the progression of atherosclerosis collagen biosynthesis and endothelial dysfunction. Therefore, this study was mainly planned to evaluate the association between the presence and severity of ED and the serum prolidase activity and serum levels of oxidative stress markers, such as total free sulfhydryl (–SH) and lipid hydroperoxide (LOOH).
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Materials and Methods |
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Erectile function was evaluated by the erectile function domain of the International Index of Erectile Function (IIEF-EF), a validated, 15-item, self-administered questionnaire. Erectile function is specifically addressed by 6 questions that form the so-called erectile function domain of the questionnaire. Each question is scored 0 to 5. ED is defined as any value less than 26 points. ED severity is classified into 3 categories based on the IIEF-5: Group I, severe (5–7 points); Group II, moderate (8–16 points); and Group III, mild (17–26 points). Height and weight were measured according to a standardized protocol. Body mass index (BMI) was calculated by dividing weight in kilograms by height in meters squared (kg/m2).
Blood Sample Collection
Blood samples were obtained after an overnight fasting state. Samples were
withdrawn from a cubital vein into blood tubes, and serum was immediately
separated from the cells by centrifugation at 3000 x g for 10
minutes, stored at –70°C, and then analyzed.
Measurement of Serum Prolidase Activity
Serum was diluted 40-fold with 2.5 mmol/L Mn2+ and 40 mmol/L
trizma HCl buffer (pH 8.0) and was preincubated at 37°C for 2 hours. The
reaction mixture containing 30 mmol/L gly-pro, 40 mmol/L trizma HCl buffer (pH
8.0), and 100 mL of preincubation serum in 1 mL was incubated at 37°C for
30 minutes. The supernatant was used for measurement of proline by the method
proposed by Myara et al
(1982), which is a
modification of the method of Chinard
(1952). Intraassay coefficient
of variation (CV) of the assay was 3.8%.
Measurement of Serum Lipid Hydroperoxide
Serum LOOH (µmol/L tBLOOH) levels were determined by the ferrous ion
oxidation-xylenol orange method as previously described
(Arab and Steghens, 2004). The
method is based on a known principle of the oxidation of Fe II to Fe III by
LOOHs under acidic conditions. CV for measurement of serum LOOH levels was
3.1%.
Measurement of Total Free Sulfhydryl Groups
Serum free sulfhydryl (–SH; mmol/L) levels were assayed according to
the method of Ellman (1959) as
modified by Hu et al (1993).
Briefly, 1 mL of buffer containing 0.1 M Tris; 10 mmol/L EDTA, pH 8.2; and 50
mL of serum was added to cuvettes, followed by 50 mL of 10 mmol/L
5,5'-dithiobis(2-nitrobenzoic acid) in methanol. Blanks were run for
each sample as a test. After incubation for 15 minutes at room temperature,
sample absorbance was interpreted at 412 nm on a Cecil 3000 spectrophotometer
(Cecil Instruments, Cambridge, United Kingdom). Sample and reagent blanks were
subtracted. The concentration of –SH groups was calculated using reduced
glutathione as the free –SH group standard, and the results were
expressed as millimoles per liter. CV for measurement of serum –SH
levels was 3.6%.
Measurement of Other Laboratory Markers
The serum levels of uric acid, creatinine, triglyceride, total cholesterol,
high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL)
cholesterol, and fasting glucose were determined using commercially available
assay kits (Abbott, Abbott Park, Illinois) with Abbott Aeroset autoanalyzer
(Abbott).
Statistical Analysis
All analyses were conducted using SPSS 11.5 (SPSS Inc, Chicago, Illinois).
Continuous variables were expressed as mean ± SD, and categoric
variables were expressed as percentages. Comparison of categoric and
continuous variables between the ED and control groups was performed using the
2 test and independent-samples t test, respectively.
Comparison of laboratory variables between the groups categorized according to
the severity of ED was performed using one-way analysis of variance (ANOVA)
with least significant difference posthoc test. The correlation between serum
prolidase activity, IIEF-EF score, and clinical and laboratory parameters was
assessed by the Pearson correlation test. To determine independent predictors
of the presence of ED, multiple logistic regression analysis was performed by
including the parameters that were significantly different between ED and
control groups. Multiple linear regression analysis was performed to identify
the independent predictors of serum prolidase activity and IIEF-EF score by
including the parameters that were correlated with serum prolidase activity
and IIEF-EF score, respectively, in bivariate analysis. Standardized
β-regression coefficients and their significance from multiple linear
regression analysis were reported. Comparison of laboratory variables between
the groups categorized according to the vascular status of ED was performed
using one-way ANOVA with least significant difference posthoc test.
Receiver-operator curve (ROC) characteristics of serum prolidase levels were
examined to identify a cutoff value to predict ED. A two-tailed P
< .05 was considered statistically significant.
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Results |
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2
= 4.277, β = 0.681, P = .059), urea (2 = 9.111,
β = 0.089, P = .03), and –SH (2 = 25.988,
β = –30.473, P = .018) levels, and serum prolidase
activity (2 = 76.533, β = 0.221, P = .004), but
not serum creatinine, HDL cholesterol, and LOOH levels, were independent
predictors of the presence of ED. Comparisons of variables according to
severity of ED are shown in Table
2. The comparison included 92 ED patients grouped into 3
categories according to the IIEF-EF scores: mild disease (n = 37), moderate
disease (n = 30), and severe disease (n = 25), in addition to 50 controls. The
lowest and highest mean serum prolidase activities were detected in control
participants and in patients with severe ED disease, respectively, and we have
shown a gradual increase in mean serum prolidase activity with increasing
severity of ED (ANOVA P < .001). Serum –SH levels of
patients with either moderate or severe disease were significantly lower than
either controls or patients with mild disease (ANOVA P < .001).
Serum LOOH levels were significantly increased in patients with moderate or
severe disease compared with controls (ANOVA P = .021). The
relationship between serum prolidase activity and clinical characteristics and
laboratory data is presented in Table
3. Serum prolidase activity was positively correlated with age,
presence of hypertension, fasting blood glucose, serum urea, creatinine, and
LOOH levels, as well as severity of ED (serum prolidase activity was inversely
correlated with IIEF-EF score; P < .05 for all;
Table 3). Additionally, serum
prolidase activity was inversely correlated with serum HDL cholesterol and
–SH levels in bivariate analysis (P < .05 for all;
Table 3). To determine
independent predictors of serum prolidase activity, a stepwise linear
regression analysis was performed by including parameters that were correlated
with serum prolidase activity in bivariate analysis. Serum HDL cholesterol
(β = –0.140, P = .024) and urea (β = 0.145,
P = .039) levels and IIEF-EF score (β = –0.320, P
< .001) were independent predictors of serum prolidase activity
(Table 3). The relationship
between IIEF-EF score and clinical characteristics and laboratory parameters
data is presented in Table 4.
IIEF-EF score was inversely correlated with age, serum triglyceride, and
creatinine levels, as well as serum prolidase activity (P < .05
for all; Table 4).
Additionally, IIEF-EF score was positively correlated with serum HDL
cholesterol and –SH levels in bivariate analysis (P < .05
for all; Table 4). To determine
independent predictors of IIEF-EF score, a stepwise linear regression analysis
was performed by including parameters that were correlated with IIEF-EF score
in bivariate analysis. Serum triglyceride (β = 0.171, P = .002),
HDL cholesterol (β = 0.176, P = .002), and –SH levels
(β = 0.266, P < .001), and serum prolidase activity (β =
–0.270, P < .001) were independent predictors of IIEF-EF
score (Table 4). CDU values
according to the vascular status of patients with ED are shown in
Table 5. Comparisons of
variables according to the vascular status of patients with ED are shown in
Table 6. The lowest and highest
mean serum prolidase activities were detected in control participants and in
patients with arterial insufficiency, respectively (ANOVA P <
.001). Serum –SH levels of patients with vasculogenic ED were
significantly lower than controls (ANOVA P < .001). Serum LOOH
levels were significantly higher in patients with vasculogenic ED compared
with controls (ANOVA P < .001). Additionally, serum prolidase
activity was inversely correlated with peak systolic blood flow velocity and
resistance index in vasculogenic ED (P < .05). The ROC
characteristics of serum prolidase activity to predict ED are presented in the
Figure. Area under the curve
was 0.78. The serum prolidase ROC curve analysis showed a sensitivity of 96%
(95% confidence interval [CI], 79.6%–99.3%) and a specificity of 71.4%
(95% CI, 49.2%–95.1%) for the detection of vasculogenic ED, with serum
prolidase activity 53.4 U/L used as the cut point. The positive predictive
value was 86% (95% CI, 65%–100%), and the negative predictive value was
90% (95% CI, 36%–100%).
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Discussion |
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LOOH is a well-known marker of oxidative stress formed from unsaturated phospholipids, glycol-lipids, and cholesterol by peroxidative reactions under oxidative stress. A considerable body of evidence implicates oxidative stress, in particular the reaction of nitric oxide (NO) and superoxide anion, as an important pathogenic element in the development of endothelial dysfunction in vascular diseases, such as diabetes, hypertension, arteriosclerosis, and hypercholesterolemia. Increased inactivation of NO by superoxide anion in conditions of increased oxidative stress creates an imbalance that leads to a deficit of endothelial-derived NO acutely and ultimate development of endothelial dysfunction. Oxidized LDL, other than membrane-bound, cholesterol-derived hydroperoxides, is the main form of LOOH to be responsible for the development of oxidative stress–related atherosclerosis and adverse cardiovascular events (Girotti, 1998). LDL peroxidation contributes to the development of atherosclerosis, and injuries to endothelial cells have a principal role in the progression of atherosclerotic lesions (Rubbo et al, 2002). Oxidized LDL has been shown to impair endothelium-dependent relaxation in the penis and may also contribute to endothelial dysfunction observed in hypercholesterolemia through an increased production of superoxide anion via uncoupling of endothelial NO synthase (eNOS) or a reduction in the eNOS cofactor BH4 (tetrahydrobiopterin) (Ahn et al, 1999).
Fibrosis of the corpora cavernosa and the media of penile arteries, involving loss of SMCs, is a highly prevalent process that underlies most cases of vasculogenic ED (Gonzales-Cadavid, 2009). The concept that a progressive fibrosis of the smooth muscle tissue within the penile corpora cavernosa is responsible for the vasculogenic ED associated with diabetes, aging, heavy smoking, and pelvic surgery has gained support during the last decade (Kovanecz et al, 2009). Histologically, this fibrotic process is characterized by the excessive deposition of collagen fibers and extracellular matrix, loss of SMCs, presumably due to a combination of a higher rate of SMC apoptosis with a reduced rate of cell proliferation, and an increase in profibrotic factors, such as transforming growth factor-β1 and reactive oxygen species (Schwartz et al, 2004). From a functional perspective, this fibrotic process leads to a decrease in the compliance of the corporal tissue after stimulation by the NO/cyclic guanosine monophosphate (cGMP) system. This inability of the corporal tissue to relax sufficiently to occlude the aggressing subtunical veins occurs in most patients with ED (Rajfer et al, 1988; Nehra et al, 1996; Lue, 1996; Metro and Broderick, 1999; Luo et al, 2007) and is termed venous leakage or corporal veno-occlusive dysfunction (CVOD). Therefore, without disregarding the potential role of endothelial dysfunction, the progressive damage of the smooth muscle tissue in the corpora cavernosa by either an acute and/or chronic process is probably the major single factor impairing erectile function in patients with ED. Because the penis is considered to be an extension of the vascular system, it is not surprising that many changes that occur within the corporal tissue are also reflected in the cardiovascular system. This helps explain why there is a strong association between ED and various cardiovascular disorders, such as hypertension, heart disease, etc. Indeed, with aging, the fibrotic changes seen in the penile corpora cavernosa resemble those seen within the arterial wall, and it has been suggested that this relative fibrosis of the media of the arterial tree (arteriosclerosis) is pathophysiologically the same disorder as CVOD, where both tissues have lost their SMCs, together with an increase in fibrosis within that part of the tissue where the SMCs are located (Aronson, 2003; Wang and Fitch, 2004; Najjar et al, 2005; Díez, 2007; Izzo and Mitchell, 2007). In general terms, aging-related changes as represented by other markers of fibrosis and oxidative stress were similar in the arterial media and the corpora cavernosa. Therefore, the study of fibrosis may provide a unifying view on the vasculogenic disorders affecting the penis. Profibrotic factors, the excessive deposit of collagen fibers and other extracellular matrix, the appearance of a synthetic cell phenotype in SMCs or the onset of a fibroblast-myofibroblast transition and, in the case of the corporal or penile arterial tissue, the reduction of the smooth muscle cellular compartment underlie vasculogenic ED. This histopathology leads either to localized plaques or nodules in penile tissues, or to the diffuse fibrosis causing impairment of tissue compliance that underlies CVOD and arteriogenic ED. The antifibrotic role of the sustained stimulation of the NO/cGMP pathway in the penis and its possible relevance to exogenous and endogenous stem cell differentiation may be interpreted to the collagen biosynthesis. The relationship between collagen and prolidase activity was observed during fibrotic processes, where an increase in prolidase activity was accompanied by an increase in tissue collagen deposition (Verit et al, 2006). The negative effect of free radicals is mediated by degradative agents, such as proteolytic enzymes, and the last step of collagen degradation is mediated by prolidase (Altindag et al, 2007). Surazynski et al (2008) pointed out that prolidase may also have a possible role in angiogenesis, depending on the fact that prolidase deficiency is associated with angiopathy. Oxidative stress resulted in collagen degradation, and this process is mediated by prolidase (Altindag et al, 2007). Moreover, the degree of severity of oxidative stress is directly correlated with the inhibition of collagen production, and prolidase is supposed to be the target enzyme of this process (Sienkiewicz et al, 2004). Yildiz et al (2008) showed that serum prolidase activity in an increasing manner was significantly associated with the presence and severity of CAD. In addition, it was suggested that hypertension and its duration are associated with increased serum prolidase activity, and it may be a marker for the follow-up of hypertensive patients (Demirbag et al, 2007).
Our results revealed that serum prolidase activity can be assessed as a predictor of vasculogenic ED. Our study is the first to address a cutoff value for serum prolidase level in vasculogenic ED. We found that a serum prolidase level of 53.4 U/L can be used to predict vasculogenic ED.
Several limitations of this study should be considered. One potential limitation of this study is the cross-sectional study design. Beyond the findings of our study, assessing serum prolidase activity in atherosclerotic plaque and in endothelial cells and evaluating the association of serum prolidase activity and the presence and the extent of atherosclerosis in other territories of arterial system, which remain to be evaluated, would better clarify the pathophysiologic role of prolidase activity in the atherosclerotic process and endothelial dysfunction. Evaluating the association of serum prolidase activity and the extent of endothelial ischemia would identify the role of endothelial ischemia in increased collagen turnover in patients with vasculogenic ED. Measuring serum and urine levels of proline or hydroxyproline would add to the value of this study; however, we did not have the opportunity to perform these measurements.
In conclusion, with the data of this study we have shown an independent relationship between increased serum prolidase activity and the presence and severity of vasculogenic ED, which may be interpreted as evidence of increased collagen turnover in vasculogenic ED. Serum prolidase activity appears to be a sensitive and specific predictor of vasculogenic ED, and for this reason it may be used in early prediction of vasculogenic ED in the male population. However, further clinical studies are needed to clarify the pathophysiologic role of serum prolidase activity in vasculogenic ED.
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References |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Altindag O, Erel O, Aksoy N, Selek S, Celik H, Karaoglanoglu M. Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis. Rheumatol Int. 2007; 27: 339 –344.[CrossRef][Medline]
Arab K, Steghens JP. Plasma lipid hydroperoxides measurement by an automated xylenol orange method. Anal Biochem. 2004; 325: 158 –163.[CrossRef][Medline]
Aronson D. Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens. 2003;21: 3 –12.[CrossRef][Medline]
Aslan M, Nazligul Y, Horoz M, Bolukbas C, Bolukbas FF, Aksoy N, Celik H, Erel O. Serum prolidase activity and oxidative status in Helicobacter pylori infection. Clin Biochem. 2007; 40: 37 –40.[CrossRef][Medline]
Cechowska-Pasko M, Palka J, Wojtukiewicz MZ. Enhanced prolidase activity and decreased collagen content in breast cancer tissue. Int J Exp Pathol. 2006; 87: 289 –296.[CrossRef][Medline]
Chinard FP. Photometric estimation of proline and ornithine.
J Biol Chem. 1952; 199: 91
–95.
Demirbag R, Yildiz A, Gur M, Yilmaz R, Elci K, Aksoy N. Serum prolidase activity in patients with hypertension and its relation with left ventricular hypertrophy. Clin Biochem. 2007; 40: 1020 –1025.[CrossRef][Medline]
Díez J. Arterial stiffness and extracellular matrix. Adv Cardiol. 2007; 44: 76 –95.[Medline]
Duong HS, Zhang QZ, Le AD, Kelly AP, Kamdar R, Messadi DV. Elevated prolidase activity in keloids: correlation with type I collagen turnover. Br J Dermatol. 2006; 154: 820 –828.[CrossRef][Medline]
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82: 70 –77.[CrossRef][Medline]
Erbagci AB, Araz M, Erbagci A, Tarakcioglu M, Namiduru ES. Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus. Clin Biochem. 2002; 35: 263 –268.[CrossRef][Medline]
Evrenkaya TR, Atasoyu EM, Kara M, Unver S, Gultepe M. The role of prolidase activity in the diagnosis of uremic bone disease. Ren Fail. 2006;28: 271 –274.[CrossRef][Medline]
Gejyo F, Kishore BK, Arakawa M. Prolidase and prolinase activities in the erythrocytes of patients with chronic uremia. Nephron. 1983;35: 58 –61.[CrossRef][Medline]
Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983; 51: 606 –607.[CrossRef][Medline]
Girotti AW. Lipid hydroperoxide generation, turnover, and effector
action in biological systems. J Lipid Res. 1998; 39: 1529
–1542.
Gonzalez-Cadavid NF. Mechanisms of penile fibrosis. J Sex Med. 2009;6(suppl 3): 353–362.[CrossRef][Medline]
Hu ML, Louie S, Cross CE, Motchnik P, Halliwell B. Antioxidant protection against hypochlorous acid in human plasma. J Lab Clin Med. 1993;121: 257 –262.[Medline]
Izzo JL Jr, Mitchell GF. Aging and arterial structure-function relations. Adv Cardiol. 2007; 44: 19 –34.[Medline]
Kovanecz I, Nolazco G, Ferrini MG, Toblli JE, Heydarkhan S, Vernet D, Rajfer J, Gonzalez-Cadavid NF. Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction. BJU Int. 2009; 103(10): 1396 –1404.[CrossRef][Medline]
Lijnen HR. Metalloproteinases in development and progression of vascular disease. Pathophysiol Haemost Thromb. 2003–2004; 33: 275 –281.[CrossRef]
Liu G, Nakayama K, Awata S, Tang S, Kitaoka N, Manabe M, Kodama H. Prolidase isoenzymes in the rat: their organ distribution, developmental change and specific inhibitors. Pediatr Res. 2007; 62: 54 –59.[CrossRef][Medline]
Lue TF. Veno-occlusive dysfunction of corpora cavernosa: comparison of diagnostic methods. J Urol. 1996; 155: 786 –787.[Medline]
Luo H, Goldstein I, Udelson D. A three-dimensional theoretical model of the relationship between cavernosal expandability and percent cavernosal smooth muscle. J Sex Med. 2007; 4: 644 –645.[CrossRef][Medline]
Maas R, Schwedhelm E, Albsmeier J, Boger RH. The pathophysiology of
erectile dysfunction related to endothelial dysfunction and mediators of
vascular function. Vasc Med. 2002; 7: 213
–225.
Metro MJ, Broderick GA. Diabetes and vascular impotence: does insulin dependence increase the relative severity? Int J Impot Res. 1999;11: 87 –89.[CrossRef][Medline]
Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: application to imminodipeptiduria. Clin Chim Acta. 1982; 125: 193 –205.[CrossRef][Medline]
Myara I, Myara A, Mangeot M, Fabre M, Charpentier C, Lemonnier A.
Plasma prolidase activity: a possible index of collagen catabolism in chronic
liver disease. Clin Chem. 1984; 30: 211
–215.
Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an
immutable cardiovascular risk factor? Hypertension. 2005; 46: 454
–462.
Nehra A, Goldstein I, Pabby A, Nugent M, Huang YH, de las Morenas A, Krane RJ, Udelson D, Saenz de Tejada I, Moreland RB. Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure. J Urol. 1996; 156: 1320 –1329.[CrossRef][Medline]
Newby AC, Southgate KM, Davies M. Extracellular matrix degrading metalloproteinases in the pathogenesis of arteriosclerosis. Basic Res Cardiol. 1994;89: 59 –70.[Medline]
Palka JA, Phang JM. Prolidase activity in fibroblasts is regulated by interaction of extracellular matrix with cell surface integrin receptors. J Cell Biochem. 1997; 67: 166 –175.[Medline]
Rajfer J, Rosciszewski A, Mehringer M. Prevalence of corporal venous leakage in impotent men. J Urol. 1988; 140: 69 –71.[Medline]
Rubbo H, Trostchansky A, Botti H, Batthyany C. Interactions of nitric oxide and peroxynitrite with low-density lipoprotein. Biol Chem. 2002;383: 547 –552.[CrossRef][Medline]
Schwartz EJ, Wong P, Graydon RJ. Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol. 2004;171: 771 –774.[CrossRef][Medline]
Senboshi Y, Oono T, Arata J. Localization of prolidase gene expression in scar tissue using in situ hybridization. J Dermatol Sci. 1996;12: 163 –171.[CrossRef][Medline]
Shah PK. Role of inflammation and metalloproteinases in plaque
disruption and thrombosis. Vasc Med. 1998; 3: 199
–206.
Shrinath M, Walter JH, Haeney M, Couriel JM, Lewis MA, Herrick AL.
Prolidase deficiency and systemic lupus erythematosus. Arch Dis
Child. 1997;76: 441
–444.
Sienkiewicz P, Pa
ka M, Paka J. Oxidative stress
induces IGF-I receptor signaling disturbances in cultured human dermal
fibroblasts. A possible mechanism for collagen biosynthesis inhibition.
Cell Mol Biol Lett. 2004; 9: 643
–650.[Medline]
Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001; 44: 129 –146.[CrossRef][Medline]
Solomon H, Man JW, Jackson G. Erectile dysfunction and the
cardiovascular patient: endothelial dysfunction is the common denominator.
Heart. 2003;89: 251
–253.
Surazynski A, Donald SP, Cooper SK, Whiteside MA, Salnikow K, Liu Y, Phang JM. Extracellular matrix and HIF-1 signaling: the role of prolidase. Int J Cancer. 2008; 122: 1435 –1440.[CrossRef][Medline]
Surazynski A, Sienkiewicz P, Wolczynski S, Palka J. Differential effects of echistatin and thrombin on collagen production and prolidase activity in human dermal fibroblasts and their possible implication in beta1-integrinmediated signaling. Pharmacol Res. 2005; 51: 217 –221.[CrossRef][Medline]
Tal R, Voelzke BB, Land S, Motarjem P, Munarriz R, Goldstein I, Mulhall JP. Vasculogenic erectile dysfunction in teenagers: a 5-year multi-institutional experience. BJU Int. 2009; 103(5): 646 –650.[CrossRef][Medline]
Verit FF, Geyikli I, Yazgan P, Celik A. Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis. Arch Gynecol Obstet. 2006; 274: 133 –137.[CrossRef][Medline]
Wang YX, Fitch RM. Vascular stiffness: measurements, mechanisms and implications. Curr Vasc Pharmacol. 2004; 2: 379 –384.[CrossRef][Medline]
Watanabe N, Ikeda U. Matrix metalloproteinases and atherosclerosis. Curr Atheroscler Rep. 2004; 6: 112 –120.[Medline]
Yildiz A, Demirbag R, Yilmaz R, Gur M, Altiparmak IH, Akyol S, Aksoy N, Ocak AR, Erel O. The association of serum prolidase activity with the presence and severity of coronary artery disease. Coron Artery Dis. 2008;19: 319 –325.[CrossRef][Medline]
Zanaboni G, Dyne KM, Rossi A, Monafo V, Cetta G. Prolidase
deficiency: biochemical study of erythrocyte and skin fibroblast prolidase
activity in Italian patients. Haematologica. 1994; 79: 13
–18.
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