Hypertension-mediated albuminuria is associated with reduced lysosomal activity in the kidney and the heart.

Recent studies suggest that expression of the transforming growth factor-beta (TGF-beta)-inducible gene-h3 (betaig-h3) and its anti-lysosomal activity may be responsible for the development of albuminuria and cardiovascular disease associated with hypertension. We evaluated the proposed linkage using the spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat models. The kidney and left ventricular weight/body weight ratios were measured and cardiac collagen deposition was analyzed by Masson's trichrome stain. Renal and cardiac TGF-beta(1) and betaig-h3 expression were determined by real-time reverse transcription-polymerase chain reaction, and renal and cardiac cathepsin B and L activities were measured as an indicator of lysosomal proteolytic activity. SHR exhibited increased levels of intact urinary albumin without significant change in total albumin (intact plus albumin-derived material) excretion. This was accompanied by renal hypertrophy, increased renal betaig-h3 expression, and reduced renal cathepsin B and L activities. At the same time, increased cardiac TGF-beta(1) and betaig-h3 expression and reduced cardiac cathepsin B activity was identified in SHR in addition to cardiac hypertrophy and increased collagen deposition. All these changes could be ameliorated with ramipril treatment. These findings implicate for the first time betaig-h3 expression and lysosomal activity as a key factor in the induction of albuminuria and cardiovascular disease associated with hypertension.

Hilliard LM ，Russo LM ，Comper WD 《-》

The effect of ramipril on albumin excretion in diabetes and hypertension: the role of increased lysosomal activity and decreased transforming growth factor-beta expression.

Russo LM ，Brammar GC ，Jerums G ，Comper WD ，Osicka TM ... -  《JOURNAL OF HYPERTENSION》

Effects of ACE inhibition and beta-blockade on plasminogen activator inhibitor-1 and transforming growth factor-beta1 in carotid glomus and autonomic ganglia in hypertensive rats.

Toblli JE ，Grana D ，Cao G ，Milei J ... -  《AMERICAN JOURNAL OF HYPERTENSION》

[Effect of perindopril on renal interstitial fibrosis of hypertension in rats].

Xu H ，Tao LJ ，Sun M 《-》

Tranilast prevents the progression of experimental diabetic nephropathy through suppression of enhanced extracellular matrix gene expression.

Akahori H ，Ota T ，Torita M ，Ando H ，Kaneko S ，Takamura T ... -  《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》