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Sex differences in distribution of cannabinoid receptors (CB1 and CB2), S100A6 and CacyBP/SIP in human ageing hearts
Żaneta Piotrowska1, Michał Niezgoda1, Wojciech Łebkowski2
1Department of Histology and Cytophysiology, Medical University of Białystok, Białystok, Poland.
Insights
This study reveals sex and age-related differences in cannabinoid receptors (CB1, CB2) and calcium-binding proteins (S100A6, CacyBP/SIP) within the human heart, impacting cardiovascular function with aging.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Gerontology
Background:
- Women exhibit longer lifespans, partly due to reduced cardiovascular complications with aging.
- Mechanisms preserving female cardiac function during aging remain unclear.
- The endocannabinoid system regulates cardiovascular function via cannabinoid receptors (CB1, CB2).
Purpose of the Study:
- To investigate sex differences in cardiac cannabinoid receptors, S100A6, and CacyBP/SIP during aging.
- To compare the expression of these proteins in the myocardium of aging men and women.
Main Methods:
- Immunohistochemical analysis of cannabinoid receptors (CB1, CB2), S100A6, and CacyBP/SIP in human heart sections.
- Gene expression analysis using real-time PCR for CB1, CB2, S100A6, and CacyBP/SIP.
- Study included organ donors aged under and over 50 years, divided by sex.
Main Results:
- CB1 and CB2 receptor expression decreased with age in cardiomyocytes.
- Sex-based differences in CB1 and CB2 expression were observed, varying with age.
- S100A6 and CacyBP/SIP levels increased with age; male hearts showed higher S100A6 but lower CacyBP/SIP than females.
- Gene expression patterns correlated with protein levels, indicating sex and age dependency.
Conclusions:
- Age and sex significantly influence the distribution and levels of cardiac cannabinoid receptors and calcium-binding proteins.
- These findings highlight interactions between aging and sex in regulating human heart function.
Background:
Women 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.
Methods:
The 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.
Results:
CB1 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.
Conclusion:
Together, 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.
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