Age and Sex Dependency of Thoracic Aortopathy in a Mouse Model of Marfan Syndrome

Thoracic aortic aneurysm is one of the manifestations of Marfan syndrome (MFS) that is known to affect men more severely than women. However, the incidence of MFS is similar between men and women. The aim of this study is to show that during pathological aortic dilation, sex-dependent severity of thoracic aortopathy in a mouse model of Marfan syndrome translates into sex-dependent alterations in cells and matrix of the ascending aorta, consequently affecting aortic biomechanics. Fibrillin1 C1041G/+ were used as a mouse model of MFS. Ultrasound measurements from 3-12 months showed increased aortic diameter in Marfan aorta with larger percent increase in diameter for males compared to females. Immunohistochemistry showed decreased contractile smooth muscle cells in Marfan aortic wall compared to healthy aorta, which was accompanied by decreased contractility measured by wire myography. Elastin autofluorescence, second harmonic generation microscopy of collagen fibers and passive biomechanical assessments using myography showed more severe damage to elastin fibers, increased medial fibrosis, and increased stiffness of the aortic wall in MFS males but not females. Male and female heterozygotes showed increased expression of Sca-1-positive adventitial progenitor cells vs. controls at young ages. In agreement with clinical data, Marfan mice demonstrate sex-dependent severity of thoracic aortopathy. It was also shown that aging exacerbates the disease state especially for males. Our findings suggest that female mice are protected from progression of aortic dilation at early ages, leading to a lag in aneurysm growth.

An international comparison of age and sex dependency of COVID-19 deaths in 2020: a descriptive analysis

The number of reported coronavirus disease (COVID-19) deaths per 100,000 persons observed so far in 2020 is described in 15 European countries and the USA as dependent on age groups and sex. It is compared with the corresponding historic all-cause mortality per year depending on age and sex observed in these countries. Some common features exist although substantial differences in age and sex dependency of COVID-19 mortality were noted between countries. An exponential increase with age is a good model to describe and analyze both COVID-19 and all-cause mortality above 40 years old, where almost all COVID-19 deaths occur. Moreover, age dependency is stronger for COVID-19 mortality than for all-cause mortality, and males have an excess risk compared with women, which is less pronounced in the higher age groups. Additionally, concerning calendar time, differences in the age and sex dependency between countries were noted with the common tendency that male excess risk for COVID-19 mortality was smaller in the second half of the year.

Heart Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 Gene Expression Associated With Male Sex and Salt-Sensitive Hypertension in the Dahl Rat

Angiotensin-converting enzyme 2 (ACE 2) in the heart including its sex dependency in the hypertensive heart, has not been much studied compared to ACE. In the present study, we used the Dahl salt-sensitive rat exposed to fructose and salt to model a hypertensive phenotype in males, females, and ovariectomized females. Blood pressure was measured by the tale-cuff technique in the conscious state. Expression of RAS-related genes ACE, ACE2, angiotensin II receptor type 1, Mas1, and CMA1 in the heart were quantified. The results revealed small but significant differences between male and female groups. The main results indicate the presence of a male preponderance for an increase in ACE and ACE2 gene expression. The results are in accordance with the role of androgens or male chromosomal complement in controlling the expression of the two ACE genes.

An international comparison of age and sex dependency of COVID-19 Deaths in 2020 - a descriptive analysis

SummaryCOVID-19 mortality, the number of reported COVID-19 deaths per 100,000 persons observed so far, is described in 15 European countries and the USA depending on age groups and sex for the full year 2020. It is contrasted to the corresponding historic all-cause mortality per year depending on age and sex observed in these countries. Although there are substantial differences in the age and sex dependency of COVID-19 mortality between countries, there are some common features: Exponential increase with age is a good model to describe and analyse both COVID-19 and all-cause mortality above an age of 40 years, where almost all COVID-19 death occur. Age dependency is stronger for COVID-19 mortality than for all-cause mortality, males have an excess risk compared to women which flattens off with increasing age. Also with regard to calendar time, there were differences in the age and sex dependency between countries with the common tendency that male excess risk of COVID-19 mortality was smaller in the second half of the year.