Excessive Sodium Intake Leads to Cardiovascular Disease by Promoting Sex-Specific Dysfunction of Murine Heart

Abstract

BackgroundGlobally, a high-salt diet (HSD) has become a threat to human health as it can lead to a high risk of cardiac damage. Although some studies investigating HSD have been carried out, the majority has been conducted in males, and there are few female-specific studies, thereby ignoring any effects of sex-specific damage on the heart. In this study, we determined how HSD induces different pathways of cardiovascular diseases through sex-specific effects on cardiac damage in mice.MethodsAn HSD murine model of male and female C57BL/6J mice was fed with sodium-rich chow (4% NaCl). After 8 weeks, cardiac tissues were collected, and the whole gene transcriptome of the hearts of male and female mice was characterized and analyzed using high-throughput RNA sequencing. Immunohistochemistry staining was used to further assess the harmful effects of HSD on protein expression of genes associated with immunity, fibrosis, and apoptosis in male and female mice.ResultsHSD drastically altered the cardiac transcriptome compared to that of the normal heart in both male and female mice and had a sex-specific effect on the cardiac composition in the transcriptome. HSD produced various differentially expressed genes and affected different KEGG pathways of the transcriptome in male and female mice. Furthermore, we found that HSD induced different pathways of cardiovascular disease in the male mice and female mice. The pathway of hypertrophic cardiomyopathy is significantly enriched in HSD-treated male mice, while the pathway of dilated cardiomyopathy is significantly enriched in HSD-treated female mice. Finally, metabolism, immunity, fibrosis, and apoptosis in the mouse heart showed sex-specific changes predicting cardiac damage.ConclusionOur results demonstrate that HSD adversely impacts cardiac structure and function by affecting the metabolism, immunity, fibrosis, and apoptosis in the murine heart and induces the mouse to suffer from sex-specific cardiovascular disease. This study provides a new perspective and basis for the differences in the pharmacology and interventional treatment of sex-specific cardiovascular diseases induced by HSD in men and women.

Are fetal microchimerism and circulating fetal extracellular vesicles important links between spontaneous preterm delivery and maternal cardiovascular disease risk?

“…Although not as common in older women as in older men, and more likely associated with peripartum cardiomyopathy, apoptosis in cardiomyocytes is a major driver of dilated cardiomyopathy. [117,118] As the name suggests, the timing of this disease is rapid as compared to heart failure seen in older women. Evidence suggests that this disease is associated with PTB, [119,120] although exact causal relationships are unclear.…”

Low-Salt Diet Regulates the Metabolic and Signal Transduction Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways

“…Careful gene expression studies related high salt consumption to transcriptomic alterations in the cardiac tissue and the occurrence of cardiovascular diseases [ 14 , 15 ]. It was reported that excessive salt specifically enriched the pathways of hypertrophic cardiomyopathy (HCM) in the male mouse, and that of dilated cardiomyopathy (DIL) in the female mouse [ 16 ]. However, hyponatremia, defined as a serum sodium of <135 mmol/L, is an independent risk factor for higher morbidity and mortality rates [ 17 ].…”

Low-salt Diet Regulates the Metabolic and Signal Transduc-tion Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways

“…Careful gene expression studies related high salt consumption to transcriptomic alterations in the cardiac tissue and the occurrence of cardiovascular diseases [14,15]. It was reported that excessive salt specifically enriched the pathways of hypertrophic cardiomyopathy (HCM) in the male mouse and that of dilated cardiomyopathy (DIL) in the female mouse [16]. However, hyponatremia, defined as a serum sodium of < 135mmol/L, is an independent risk factor for higher morbidity and mortality rates [17].…”