Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Figure 1. Comparison of Kaplan–Meier survival curves during 8 weeks follow-up after TAC. Female C57BL/6N TAC mice (black line) and female C57BL/6N apo E−/− TAC mice (red line) are compared. The time-point of 0 days corresponds to the induction of TAC at the age of 14 weeks. Comparison of survival curves was performed by log-rank test.

Figure 2. Separation of lipoproteins by gel filtration. Cholesterol lipoprotein profile in female C57BL/6N and female C57BL/6N apo E−/− mice. Plasma samples were fractionated on a Superdex® Gel Filtration Column (Sigma, St. Louis, MO, USA). Fractions 12 to 32 contain non-HDL whereas HDL is comprised in fraction 33 to 45.

Figure 3. Left coronary artery sections illustrating coronary artery remodeling and coronary atherosclerosis. Representative Sirius Red-stained sections of the left coronary artery of female C57BL/6N sham mice (a), female C57BL/6N apo E−/− sham mice (b), female C57BL/6N TAC mice (c), and female C57BL/6N apo E−/− TAC mice (d). The media is demarcated by the internal elastic lamina (IEL) and the external elastic lamina (EEL). Atherosclerosis is present in intimal tissue within the IEL. The scale bar represents 50 µm.

Figure 4. Cardiac hypertrophy and heart failure after TAC. Body weight (panel (a)), tibia length (panel (b)), heart weight (panel (c)), heart weight/tibia length (panel (d)), left ventricular weight (panel (e)), right ventricular weight (panel (f)), lung weight (panel (g)), and liver weight (panel (h)) in female C57BL/6N sham mice (n = 16), female C57BL/6N apo E−/− sham mice (n = 9), female C57BL/6N TAC mice (n = 14), and female C57BL/6N apo E−/− TAC mice (n = 11). Sham mice are represented by open bars whereas TAC mice are represented by closed bars. C57BL/6N mice are represented in black whereas C57BL/6N apo E−/− mice are represented in red.

Figure 5. Histological analysis of pathological hypertrophy after TAC. Myocardial capillary density (panel (a)), interstitial fibrosis (panel (b)), and perivascular fibrosis (panel (c)) in female C57BL/6N sham mice, female C57BL/6N apo E−/− sham mice, female C57BL/6N TAC mice, and female C57BL/6N apo E−/− TAC mice. Representative photomicrographs show Sirius Red-stained interstitial collagen viewed under polarized light (panel (d)) and CD31-positive capillaries (panel (e)). The scale bar represents 50 µm.

Figure 6. Quantification of oxidative stress in sham mice and in TAC mice. Sham mice and TAC mice are indicated by open bars and closed bars, respectively. C57BL/6N mice are represented in black whereas C57BL/6N apo E−/− mice are represented in red. Plasma TBARS expressed as plasma malondialdehyde equivalents (panel (a)). Percentage of 3-nitrotyrosine-positive area in the myocardium (panel (b)). Quantifications in panel (a,b) were performed in 10 female C57BL/6N sham mice, 10 female C57BL/6N apo E−/− sham mice, 21 female C57BL/6N TAC mice, and 31 female C57BL/6N apo E−/− TAC mice. Representative photomicrographs showing myocardial sections stained for 3-nitrotyrosine (panel (c)). The scale bar represents 50 µm.