A_2A adenosine receptor-mediated increase in coronary flow in hyperlipidemic APOE–knockout mice

Figures & data

Table 1 Baseline functional data of C57BL/6 J (WT), APOE and APOE-HFD

	WT (n = 16)	APOE (n = 15)	APOE-HFD (n = 14)
Body weight (g)	28.40 ± 4.57	26.01 ± 3.38	28.31 ± 5.35
Heart weight (mg)	157.40 ± 22.70	150.60 ± 21.85	171.59 ± 24.38
Heart-to-body weight ratio (%)	0.53 ± 0.12	0.53 ± 0.04	0.58 ± 0.08
Coronary flow (mL/min/g)	13.23 ± 3.58	13.22 ± 2.78	12.37 ± 4.76
Heart rate (beat/min)	381.51 ± 34.25	372.39 ± 22.50	369.06 ± 34.18
Developed pressure (mm Hg)	141.61 ± 22.00	118.46 ± 30.88	123.62 ± 16.66

Notes: All values are means ± SEM; functional parameters were measured after 30 min of normothermic aerobic perfusion using a standard Langendorff preparation; P < 0.05.

Abbreviations: APOE, apolipoprotein E knockout; APOE-HFD, APOE fed high-fat diet; n, number of hearts; SEM, standard error of the mean; WT, wild type.

Figure 1 Concentration–response curves for coronary flow (A), heart rate (B), and left ventricular developed pressure (C) for NECA in isolated perfused hearts from WT apolipoprotein E–knockout mice, and APOE-HFD.

Notes: *Significant difference from WT; ^#significant difference from APOE.
Abbreviations: APOE, apolipoprotein E; APOE-HFD, APOE fed high-fat diet; HR, heart rate; LVDP, left ventricular developed pressure; NECA, 5′-N-ethylcarboxamide adenosine; WT, wild type.

Figure 2 Concentration–response curves for coronary flow (A), heart rate (B), and LVDP (C) for CGS-21680 (CGS) in isolated perfused hearts from WT, APOE, and APOE-HFD.

Notes: *Significant difference from WT; ^#significant difference from APOE.
Abbreviations: APOE, apolipoprotein E; APOE-HFD, APOE fed high-fat diet; LVDP, left ventricular developed pressure; WT, wild type.

Figure 3 Concentration–response curves for coronary flow (A), Heart rate (B), and LVDP (C) for CCPA with or without 1 µM SCH-58261 (SCH) in isolated perfused hearts from WT and APOE-HFD.

Notes: *Significant difference from WT; ^#significant difference from WT+SCH; ^$significant difference from APOE-HFD.
Abbreviations: APOE, apolipoprotein E; APOE-HFD, APOE fed high-fat diet; CCPA, 2-chloro-N6-cyclopentyl-adenosine; LVDP, left ventricular developed pressure; WT, wild type.

Figure 4 Concentration–response curves for changes in isometric tension produced by NECA in isolated aorta from WT, APOE, and APOE-HFD (A). Responses to 1 µM acetylcholine after preconstriction with 0.1 µM phenylnephrine in aortas from WT, APOE, and APOE-HFD (B).

Notes: *Significant difference from WT; ^#significant difference from APOE.

Abbreviations: APOE, apolipoprotein E; APOE-HFD, APOE fed high-fat diet; NECA, 5′-N-ethylcarboxamide adenosine; WT, wild type.

Figure 5 A representative A_2A AR Western blot (A) and the densitometric analysis (B) of aortas from WT, APOE, and APOE-HFD. β-actin was used as a loading control.

Note: *Significant difference from WT.
Abbreviations: APOE, apolipoprotein E; APOE-HFD, APOE fed high-fat diet; A_2A AR, A_2A adenosine receptor; WT, wild type.