Sex-Differences in Vascular Reactivity of Internal Mammary Artery and Subcutaneous Microvessels

Abstract

S8Heart, Lung and Circulation CSANZ 2012 Abstracts 2012;21:S1-S142 signalling may provide evidence for the development of cardiac-and/or gender-specific MR therapies. The aim of the current study was to (i) characterise the role of cardiomyocyte MR signalling in cardiac structural and functional remodelling, (ii) identify the signalling pathways regulated by cardiomyocyte MR and (iii) identify sex-specific regulation of those pathways using selective cardiomyocyte MR knockout mice (myo-MRKO). Hearts from wild-type (WT) and myo-MRKO were excised and subjected to 20 min global ischaemia using the Langendorff isolated mouse heart system (n = 4-9 per group, 16 weeks old). There were no differences in basal cardiac function between WT and myo-MRKO mice. Both male and female myo-MRKO hearts had greater cardiac function post ischaemia/reperfusion compared to WT. Recovery of left ventricular developed pressure (% basal) in male hearts was greater than females (male: WT 59.09 ± 8.86 mmHg, myo-MRKO 85.21 ± 6.09 mmHg, female: WT 40.55 ± 3.17 mmHg, myo-MRKO 66.38 ± 5.99 mmHg, p < 0.05). This sex response challenges conventional expectation that female hearts are protected from ischaemic injury. Preliminary data from male mice treated with DOC/salt for eight weeks show greater function at baseline compared to untreated mice (WT: untreated 88.41 ± 3.89 mmHg, DOC/salt 103.14 ± 2.44 mmHg, myo-MRKO: untreated 86.49 ± 4.26 mmHg, DOC/salt 96.47 ± 7.62 mmHg, p < 0.05) and no differences between treatment groups at end of reperfusion. These data demonstrate a key role for cardiomyocyte MR signalling in acute ischaemic injury. Ongoing studies are investigating cardiomyocyte MR signalling in ischaemia/reperfusion injury pathways in disease states. http://dx. We investigated whether macrophage migration inhibitory factor (MIF); a pro-inflammatory cytokine, promotes inflammation and exacerbates cardiac injury following myocardial infarction (MI).MIF knockout (MIFKO) and wild type (WT) mice were subjected to coronary artery occlusion. Within one week after MI, incidence of cardiac rupture was higher in WT than in MIFKO mice (69% vs. 29%, P = 0.002), which was associate with a higher density of CD45+ cells at day-3 (1213 cells/mm vs. 612 cells/mm) and upregulated expression of IL-1␤ and MCP-1 at 24 h post-MI. Further MMP-9 and -2 activities at day-3 and day-7 were also significantly higher in WT mice, respectively. To differentiate the role of MIF derived from cardiomyocytes or leukocytes, we generated chimeric mice via bone marrow transplantation (BMT), i.e. WT mice received BMT from MIFKO (WT KO ) and MIFKO mice received BMT from WT mice (KO WT ).Compared to WT KO counterparts, KO WT mice post-MI presented a higher incidence of cardiac rupture (40% vs. 10%), a greater CD45+ cell infiltration, reduced fractional shortening (16% vs. 25%) and enlarged ventricular diameter size measured by echocardiography. Moreover, histological analysis demonstrated a large fraction of the necrotic myocardium (30% vs. 18%), decreased collagen deposition (3...