Gelatinase activity is induced in renal vascular lesions of rats with malignant hypertension

Abstract We previously reported a RNASeq analysis comparing kidney injury in malignant 2-kidney-1-clip hypertension versus the “benign” form of hypertension. RNAseq pointed to differential expression of many matrix metalloproteases (MMPs). We now investigated the regulation of MMP expression, immunohistochemistry and gelatinase activity in more detail. Mean blood pressure was elevated in benign hypertension (188 ± 10 mmHg) and even more pronounced in malign hypertension (236 ± 4 mmHg), compared to sham operated controls (128 ± 9mmHg). MMP2, 7, 12, 16 and 19 expression was significantly higher in malignant compared to non-malignant hypertension. The only exception was MMP9 mRNA which decreased by 0.2-fold. Gelatinase activity was detected in vascular lesions of malignant hypertension in kidneys exposed to high blood pressure. The number of gelatinase activity lesions correlated with MMP2 expression. There was no gelatinase activity in shams, or in left (post-stenotic) kidneys of hypertensive rats. MMP2 staining was detected at vascular lesions of malignant hypertensives. MMP9 staining was observed in tubules, interstitial cells, and intact vessels but absent from malignant vascular lesions. TIMP1 and 2 were detected in tubular cells. Thus, in malignant hypertension, most MMPs are upregulated. The gelatinases MMP2 and MMP9 exhibited a strikingly divergent regulation, with MMP2 localizing to malignant vascular lesions with gelatinase activity.