title: Myocardial infarction worsens glomerular injury and microalbuminuria in rats with pre-existing renal impairment accompanied by the activation of ER stress and inflammation.
abstract: Deterioration of renal function occurs after chronic heart failure in approximately one-third of patients, particularly in those with pre-existing renal impairment such as diabetic nephropathy. Impaired renal function in these patients is always associated with a worse prognosis. However, the mechanisms underlying such deterioration of renal function are still largely unknown. In three separate protocols, we compared 1) sham operation (Ctr, n = 10) with surgically induced myocardial infarction (MI, n = 10); 2) unilateral nephrectomy (UNX, n = 10) with UNX + MI (n = 10); and 3) STZ-induced type 1 diabetes (DB, n = 10) with DB + MI (n = 10). The differences between combined injury models (UNX + MI, DB + MI) and simple MI were also examined. Renal remodeling, function, ER stress (CHOP and GRP78) and inflammation (infiltration of inflammatory cells, NF-κB p65) were evaluated 12 weeks after MI. In common SD rats, MI activated less glomerular ER stress and inflammation, resulting in a minor change of glomerular remodeling and microalbuminuria. However, MI significantly increased the glomerular expression of GRP78 and CHOP in UNX and DB rats. In addition, it also promoted the infiltration of CD4+ T cells, particularly inflammatory cytokine (IFN-γ, IL-17, IL-4)-producing CD4+ T cells, and the expression of NF-κB p65 in the glomeruli. By contrast, significant glomerular fibrosis, glomerulosclerosis, podocyte injury and microalbuminuria were found in rats with UNX + MI and DB + MI. MI significantly increased chronic glomerular injury and microalbuminuria at 12 weeks in rats with pre-existing renal impairment, i.e., UNX and DB, but not common SD rats. These changes were accompanied by increased glomerular ER stress and immune-associated inflammation.
authors.affiliation: Department of Cardiology, Shanghai Sixth Hospital, Shanghai Jiaotong University School of Medicine, NO 600, Street Yishan, Shanghai, 200233, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Dong
authors.forename: Penglong
authors.initials: P
authors.lastname: Wu
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Ping
authors.initials: P
authors.lastname: Xin
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D059865:Endoplasmic Reticulum Stress; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats