Introduction:

Severe and symptomatic aortic valve stenosis (AS) has a high mortality of 50% in the course of 2 years. There are several metabolic risk factors, which are known to contribute to progression of AS. However, the SARS-CoV-2 pandemic made it clear, that mental health in general is an important factor, especially in the elderly. Mental health has physiological effects on the body, but its impact on the development of AS remains unclear. 

The present study investigates the effects of social deprivation in the development of AS in mice.

Methods:

C57BL/6J wild-type mice were assigned to three groups: 1. AS-ISO: isolation and aortic valve stenosis (n=20); 2. sham-ISO: isolation and sham procedure (n=10); 3. AS-Co: aortic valve stenosis (n=15). AS was induced via wire injury and observed for 6 weeks. ISO mice were housed isolated three weeks before wire injury and till the end of the experiment. Body parameters were measured weekly. Echocardiography was obtained every two weeks. Moreover, activity and sucrose preference were objectified. All animal experiments were performed according to "Principles of laboratory animal care", institutional guidelines and the German animal protection law. 

Hearts were analysed histologically by staining (HE, von Kossa, Pico-Sirius-Red and CD68). Furthermore, faeces was tested for corticosterone levels.

Results:

At baseline body weight (BW) and systolic blood pressure (SBP) were similar between groups (BW in g: AS-ISO 23.2 (n=13), sham-ISO 22.8 (n=10), AS-Co 22.5 (n=5); SBP in mmHg: AS-ISO 113 (n=13), sham-ISO: 109 (n=10), AS-Co 109 (n=5)). 
Due to wire injury the mean pressure gradient (MPG) rose reaching highest levels in AS-ISO after 6 weeks (Fig 1: MPG (week 6) in mmHg: AS-ISO 5.92 (n=20), sham-ISO 1.25 (n=10) and AS-Co 3.04 (n=15), p<0.05). Histologically, aortic valves were slightly larger (AS-ISO: 188,186 µm² vs AS-Co: 166,700 µm², p=ns) and more collagen fibers could be seen in the Sirius-Red staining (AS-ISO: 12,736 µm² vs AS-Co: 2,721 µm², p<0.05).

In addition, body weight gain and blood pressure differed 6 weeks after wire injury (BW gain in g: AS-ISO 2.29 (n=12), sham-ISO 2.45 (n=10), AS-Co 3.36 (n=5), p<0.05); SBP in mmHg: AS-ISO 117 (n=12), sham-ISO: 116 (n=10), AS-Co 109 (n=4), p<0.05). Furthermore, isolated mice reduced their activity (activity (AUC): AS-ISO: 9686.5 (n=8), sham-ISO: 10192.6 (n=8), AS-Co: 12460 (n=8), p<0.05), whereas no difference in sucrose preference could be detected. Corticosterone levels differed significantly (AS-ISO: 98,7 pg/mL vs AS-Co: 69,6 pg/mL, p<0.05).

Conclusion:

In C57BL/6J wild-type mice social deprivation leads to lower activity, higher blood pressure and corticosterone levels in the course of six weeks after induction of AS. The mean pressure gradients are significantly higher in these mice. Therefore, the aortic valve areas are slightly larger. Moreover, increased fibrosis is detectable. These findings show an impact of social deprivation and should be reevaluated on longer time scales.