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Transforming growth factor beta in hypertensives with cardiorenal damage
1Division of Nephrology, San Jorge General Hospital, Huesca, Spain.
Insights
Essential hypertension is linked to increased transforming growth factor beta-1 (TGF-beta(1)) and abnormal collagen type I metabolism, causing cardiorenal damage. Losartan treatment improved these markers in responders, suggesting a protective effect.
Area of Science:
- Cardiology
- Nephrology
- Biochemistry
Background:
- Essential hypertension is associated with cardiorenal damage.
- Transforming growth factor beta-1 (TGF-beta(1)) and collagen type I metabolism are implicated in hypertensive organ damage.
- Microalbuminuria and left ventricular hypertrophy are key indicators of hypertensive cardiorenal damage.
Purpose of the Study:
- To investigate the relationship between TGF-beta(1), collagen type I metabolism, microalbuminuria, and left ventricular hypertrophy in essential hypertension.
- To determine if losartan's beneficial effects on microalbuminuria and left ventricular hypertrophy are linked to changes in TGF-beta(1) and collagen type I metabolism.
Main Methods:
- Cross-sectional study comparing 30 normotensive controls with 30 hypertensive patients (with or without microalbuminuria/left ventricular hypertrophy).
- Measurements included serum TGF-beta(1), collagen type I synthesis (CICP), and degradation (CTCI) markers.
- Hypertensive patients received 6 months of losartan treatment, with responders and non-responders analyzed separately.
Main Results:
- Hypertensive patients with microalbuminuria and left ventricular hypertrophy (Group B) showed elevated TGF-beta(1), increased collagen type I synthesis, and a higher synthesis/degradation ratio compared to normotensives and hypertensive patients without these complications (Group A).
- Losartan treatment reduced TGF-beta(1), normalized collagen type I metabolism, and improved cardiorenal parameters in responders, but not in non-responders.
- Responders had greater angiotensin II type 1 receptor blockade than non-responders.
Conclusions:
- An association exists between elevated TGF-beta(1), increased collagen type I synthesis, and cardiorenal damage in essential hypertension.
- Losartan's ability to reduce TGF-beta(1) and normalize collagen type I metabolism may contribute to its protective effects on the heart and kidneys in a subset of hypertensive patients.
Abstract:
We investigated whether a relationship exists between circulating transforming growth factor beta -1 (TGF-beta(1)), collagen type I metabolism, microalbuminuria, and left ventricular hypertrophy in essential hypertension and whether the ability of the angiotensin II type 1 receptor antagonist losartan to correct microalbuminuria and regress left ventricular hypertrophy in hypertensives is related to changes in TGF-beta(1) and collagen type I metabolism. The study was performed in 30 normotensive healthy controls and 30 patients with never-treated essential hypertension classified into 2 groups: those with microalbuminuria (urinary albumin excretion >30 and <300 mg/24 h) associated with left ventricular hypertrophy (left ventricular mass index >116 g/m(2) for men and >104 g/m(2) for women) (group B; n=17) and those without microalbuminuria or left ventricular hypertrophy (group A; n=13). The measurements were repeated in all patients after 6 months of treatment with losartan (50 mg once daily). The serum concentration of TGF-beta(1) was measured by a 2-site ELISA method, and the serum concentrations of carboxy-terminal propeptide of procollagen type I (a marker of collagen type I synthesis) and carboxy-terminal telopeptide of collagen type I (a marker of collagen type I degradation) were measured by specific radioimmunoassays. The duration of hypertension and baseline values of blood pressure were similar in the 2 groups of patients. No differences in serum TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and carboxy-terminal telopeptide of collagen type I were found between normotensives and group A of hypertensives. Serum TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and the ratio of carboxy-terminal propeptide of procollagen type I to carboxy-terminal telopeptide of collagen type I were increased (P<0.05) in group B of hypertensives compared with group A of hypertensives and normotensives. No differences in carboxy-terminal telopeptide of collagen type I were found among the 3 groups of subjects. After treatment with losartan, microalbuminuria and left ventricular hypertrophy persisted in 6 patients (then considered nonresponders) and disappeared in 11 patients (then considered responders) from group B. Compared with nonresponders, responders exhibited similar control of blood pressure and higher (P<0.05) blockade of angiotensin II type 1 receptors (as assessed by a higher increase in plasma levels of angiotensin II). Whereas TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and the ratio of carboxy-terminal propeptide of procollagen type I to carboxy-terminal telopeptide of collagen type I decreased (P<0.05) in responders, no changes in these parameters were observed in nonresponders. These findings show that an association exists between an excess of TGF-beta(1), stimulation of collagen type I synthesis, inhibition of collagen type I degradation, and cardiorenal damage in a group of patients with essential hypertension. In addition, our results suggest that the ability of losartan to blunt the synthesis of TGF-beta(1) and normalize collagen type I metabolism may contribute to protect the heart and the kidney in a fraction of patients with essential hypertension.