Abstract
BackgroundWomen live about 4 years longer due to lower prevalence of cardiovascular complication with ageing. However, the mechanisms involved in the preservation of heart functionality in women have not been fully elucidated.The endocannabinoid system fulfils a significant role in the regulation of cardiovascular system functioning. Cannabinoids, acting through specific receptors (CB1 and CB2), influence on blood pressure, heart rate and myocardial contractility. The function of cardiac muscle cells is strictly dependent on calcium ions. Calcium homeostasis in cardiomyocytes is subjected to complex regulation via calcium-binding proteins. Among them, increasing attention has been paid to the recently discovered S100A6 and CacyBP/SIP.In order to better understand sex differences in the regulation of cardiomyocyte function during ageing, we undertook the present research aimed at immunohistochemical identification and comparative evaluation of cannabinoid receptors, S100A6 and CacyBP/SIP, in the myocardium of ageing men and women.MethodsThe study was conducted on the hearts of 12 men and 10 women (organ donors) without a history of cardiovascular disease. The subjects were divided into two age groups: subjects older than 50 years and subjects under 50 years old. Paraffin heart sections were processed by immunohistochemistry for detection of cannabinoids receptors, S100A6 and CacyBP/SIP. In the heart samples from each study, participant’s expression of genes coding for CB1, CB2, S100A6 and CacyBP/SIP using real-time PCR method was measured.ResultsCB1 and CB2 immunoreactivity in the cytoplasm of cardiomyocytes in the heart of subjects over 50 was weaker than in younger individuals. In the heart of younger men, CB1-immunoreactivity was weaker and CB2-immunoreaction was stronger compared to women. In the hearts of older men, the CB1-immunostaining was more intense and CB2-immunoreactivity was weaker than in women. Immunodetection of CB1 shoved the presence of receptor in the intercalated discs, but only in the hearts of individuals over the 50 years old. In the hearts of older individuals, stronger immunolabelling was observed for S100A6 and CacyBP/SIP. Male hearts had greater S100A6-immunoreactivity (both age groups) but less CacyBP/SIP immunostaining (individuals over 50 years) compared to the age-matched women. The expression of genes coding CB1, CB2, S100A6 and CacyBP/SIP in the human heart was sex and age-dependent. Observed changes between men and women as well as between subject under and over 50 years were consistent with immunohistochemically stated changes in peptide content.ConclusionTogether, the data presented here indicate a close interaction between ageing and sex on the distribution and levels of cannabinoid receptors (CB1, CB2), S100A6 and CacyBP/SIP in the human heart.
Highlights
Women live about 4 years longer due to lower prevalence of cardiovascular complication with ageing
The performed immunohistochemical tests revealed a positive reaction of CB1, CB2 receptors, S100A6 and CacyBP/SIP in the hearts of all studied men and women, the density and intensity of reactions varied between the sexes and age groups (Figs. 2, 3, 4 and 5)
In the hearts of younger men, CB1-immunoreactivity was weaker and CB2-immunoreaction was stronger compared to women, but in older individuals, the reverse was observed—greater CB1-immunostaining and less intense CB2-immunoreactivity in men than in women
Summary
Women live about 4 years longer due to lower prevalence of cardiovascular complication with ageing. Cannabinoids, acting through specific receptors (CB1 and CB2), influence on blood pressure, heart rate and myocardial contractility. In order to better understand sex differences in the regulation of cardiomyocyte function during ageing, we undertook the present research aimed at immunohistochemical identification and comparative evaluation of cannabinoid receptors, S100A6 and CacyBP/SIP, in the myocardium of ageing men and women. Stimulation of the CB1 receptor results in the weakening of cardiomyocyte contractility, while activation of the CB2 receptor increases the force of cardiac muscle cells contraction [2]. A number of experimental data have revealed a significant impact of cannabinoids on cardiomyocyte survivability and their involvement in histopathological changes in the heart [3,4,5,6,7,8,9,10,11]. Research on rodent models of cardiomyopathy has demonstrated that the activation of the CB1 receptor triggers cardiomyocyte injury, augments collagen deposition and cardiomyocyte overgrowth whereas CB2 receptor pathways evoke cardioprotective, antifibrotic and antihypertrophic action [3,4,5,6,7,8,9,10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
