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International journal of cardiology

Myocardial infarction accelerates glomerular injury and microalbuminuria in diabetic rats via local hemodynamics and immunity.


PMID 25464495

Abstract

Clinically, approximately one-third of patients with chronic heart failure (CHF) exhibit some degree of renal dysfunction. This renal dysfunction is referred to as cardiorenal syndrome (CRS) and plays an important role in the poor prognosis of CHF. Mounting evidence suggests that diabetes is the most common underlying risk factor for CRS. However, the underlying pathophysiological mechanisms are poorly understood. We performed the following comparisons in two separate protocols: 1) surgically induced myocardial infarction rats (MI, n=10), sham operation rats (Ctr, n=10) and MI rats treated with Fasudil, a Rho-kinase inhibitor (MI+Fas, n=9); and 2) STZ-induced type 1 diabetic rats (DB, n=10), DB+MI rats (n=10) and DB+MI rats treated with Fasudil (DB+MI+Fas, n=9). Renal hemodynamics and vasoconstrictor reactivity were evaluated using the DMT myograph system. Renal immunity was evaluated by flow cytometry, electron microscopy, immunofluorescence, etc. Twelve weeks after the operation, compared with DB or MI rats, DB+MI rats exhibited the following characteristics: 1) significantly increased glomerular enlargement, fibrosis, glomerulosclerosis, podocyte injury and microalbuminuria; 2) significantly increased vasoconstrictor reactivity of the renal interlobular arteries and renal venous pressure; 3) significantly increased infiltration of CD₃+ and CD₄+ T cells and decreased Treg/Th17 ratios; and 4) significantly increased glomerular deposition of IgG and C₄. In contrast, rats with MI only showed mildly accelerated glomerular remodeling and microalbuminuria, with little change in renal hemodynamics and immunity. Fasudil treatment significantly improved the renal lesions in DB+MI rats but not MI rats. Post-MI cardiac dysfunction significantly accelerated glomerular remodeling, podocyte injury and microalbuminuria in STZ-induced diabetic rats. These changes were accompanied by altered local hemodynamics and immunity.