Age- and Phenotype-Dependent Changes in Circulating MMP-2 and MMP-9 Activities in Normotensive and Hypertensive Rats

Abstract

Matrix metalloproteinases (MMPs) are important in the pathogenesis of numerous diseases. The present study aimed to monitor the activation of MMP-2 and MMP-9 in spontaneously hypertensive rats (SHR) and their normotensive counterparts—Wistar-Kyoto rats (WKY). The animals were divided according to age (7, 20, and 52 weeks) and phenotype into: WKY-7, WKY-20, WKY-52, SHR-7, SHR-20 and SHR-52 groups. MMP plasma activities were determined by gelatine zymography. We monitored selected parameters of oxidative stress and antioxidant status. N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined as a marker of heart function and neurohumoral activation. SHR-7 showed higher MMP-2 activity compared with WKY-7, while SHR-52 showed lower MMP-2 and MMP-9 activities compared with WKY-52. Examining age-dependent changes in MMP activities, we found a decrease in MMP-2 activity and increase in MMP-9 activity with increasing age in both phenotypes. Parameters of oxidative stress and antioxidant status as well as NT-proBNP levels were not significantly worsened due to aging in SHR. Our results suggest that hypertension is accompanied by varying MMP activation during aging. The results of our study may indicate that MMP-2 inhibition is therapeutically applicable during the development of hypertension, while in developed, stabilized and uncomplicated hypertension, systemic MMP-2 and MMP-9 inhibition may not be desirable.

Age- and Hypertension-Related Changes in NOS/NO/sGC-Derived Vasoactive Control of Rat Thoracic Aortae

“…In our recent study, we reported that the plasma concentration of advanced glycation end-products (AGEs) was stably decreased in 20- and 52-week-old WKYs compared to 7-week-old WKYs; however, in SHRs, it was decreased only in 20-week-old SHRs, and there was no difference between the strains. We also reported that fructosamine concentrations were not significantly different between these individual age groups when expressed in molar concentration to gram of proteins [ 24 ]. On the other hand, we found a decreased superoxide production with age in SHRs, while in WKYs, superoxide production was comparable between the age groups.…”

Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

“…Ang II is well-known and potent stimulator of inflammatory response in the organism [ 39 ]. The higher Ang II concentration can be related, at least partially, to increased plasma MMP-9 activity in both zofenopril-treated groups, as MMP-9 is produced mainly by activated immune cells, mostly macrophages [ 26 ].…”

“…Markers of oxidative stress, antioxidant status, carbonyl stress, protein oxidation, and lipid peroxidation were determined in plasma samples, according to Kollarova et al [ 26 ]. Spectrophotometric and fluorescent analyses were performed using a TecanSafire II Instrument (Grödig, Austria) and all chemicals used were purchased from the company Sigma-Aldrich (Steinheim, Germany).…”

“…Zymography is a semi-quantitative method for determining the activity of matrix metalloproteinases. The detailed method was described elsewhere [ 26 ]. The activities of circulating MMP-9 in plasma samples were detected by gelatin zymography in sodium dodecyl sulfate polyacrylamide gel (10%) with incorporated gelatin as a substrate (2 mg/mL).…”

Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets

“…Taken together, concomitant administration of MMPI and statins appears to be a promising therapeutic approach for future studies. The MMPs were investigated in the following research article by Kollarova et al [ 7 ]. The authors found elevated levels and activities of MMP-2 in hypertension-induced vascular remodeling.…”