Haemodynamic and vascular parameters.

<p>* indicates variables analysed by Mann-Whitney U test.</p

Statistical analyses of systolic blood pressure and vascular parameters.

<p>Statistical analyses of systolic blood pressure and vascular parameters.</p

Cardiac mass, structure and function parameters.

<p>* indicates variable analysed by Mann-Whitney U test.</p

Figure 1

<p>A–B. Scout cardiovascular magnetic resonance image of thoracic aorta demonstrating the planning of a transverse section through proximal descending aorta at the level of the right pulmonary artery. <b>C.</b> Arterial stiffness equations. Area(s) = systolic area, area(d) = diastolic area, ΔP = SBP-DBP, ρ = blood density (1059 kg.m⁻³).</p

Statistical analyses of cardiac mass.

<p>Statistical analyses of cardiac mass.</p

Participant characteristics.

<p>Participant characteristics.</p

Optimal dose of Domain V in cardiac IRI.

(A) C57BL/6 WT mice were treated with control or escalating doses of rhDomain V (n = 7) and assayed for troponin I by ELISA. (B) Mice treated with rhDomain V 40 μM (n = 7) had lower levels of apoptosis compared with control (n = 7). (C) Representative image from within the AAR showing apoptotic cells using the Deadend Fluorometric TUNEL system in a mouse treated with sham LAD ligation, (D) saline and (E) rh Domain V. Images obtained using a Zeiss AxioVert A1 light microscope. DV = Domain V. Points represent number of apoptotic cells in individual mouse cardiac tissue. The horizontal line for each group represents the mean.</p

Infarction size in C57BL/6 WT mice.

(A) Representative images of myocardial infarction in a mouse treated with control after 30 min ischemia and 24 h reperfusion. Section of myocardium at the mid papillary level stained with Evans Blue and 1% triphenyl-2,3,4- tetrazolium-chloride for 20 min at 37°C. The area stained blue with Evans Blue represents the non AAR (white arrow). The remaining area consists of myocardial infarction staining pale (black arrow) and the surrounding AAR that did not sustain myocardial necrosis. (B) Representative image of myocardial infarction in a mouse treated with rhDomain V. The pale staining area of infarction (black arrow) is significantly smaller than control. Consequently the extent of salvaged myocardium (orange arrow) is significantly larger. Sections photographed using Canon EOS 600D camera with Canon EF 100 mm lens and Macro ring lite MR-14Ex light source. (C) Points representing myocardial infarction size defined by 1% TTC staining. Mice treated with sham LAD occlusion demonstrated no myocardial infarction (n = 3). Control groups treated with normal saline 100μL, no treatment or human β2GPI all had similar infarction size. Mice treated with rhDomain V had a significant reduction in infarction size (n = 8 per group). AAR; Area at Risk. Individual points represent infarct size as a % of AAR of a single mouse. The horizontal line for each study group represents the mean.</p

Domain V of β2GPI binds neoepitopes on cardiac ischemic tissue inhibiting IgM NAb binding.

(A) Natural antibodies can bind multiple different epitopes in the setting of cardiac IRI including non-muscle myosin II and β2GPI bound to anionic phospholipids. Domain I of endogenous β2GPI is exposed upon binding of its Domain V to damaged endothelium in the setting of IRI. (B) Domain V binds neoepitopes exposed on the surface of damaged cardiac tissue. This has two effects, prevention of exposure of the Domain I cryptic epitope and binding of anti-β2GPI NAbs. It also prevents other NAbs binding to multiple non-β2GPI neoepitopes.</p

Serum β2GPI levels after cardiac IRI. Serum total β2GPI levels in mice 24 h after cardiac IRI.

<p>NT = No treatment. rhβ2GPI = recombinant human β2GPI. Domain V = recombinant human Domain V. Horizontal line for each group represents mean.</p