High salt intake as a multifaceted cardiovascular disease: new support from cellular and molecular evidence

Baldo, Marcelo Perim; Rodrigues, Sérgio Lamêgo; Mill, José Geraldo

doi:10.1007/s10741-015-9478-7

Cited by 33 publications

(32 citation statements)

References 144 publications

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“…A multi-factorial etiology including, chemical carcinogens, infections and diet have been suggested to play an important role in chronic inflammation. Several epidemiological studies have demonstrated that high salt (sodium chloride) diet correlated with several chronic inflammatory diseases [35, 36]. Other than in gastric cancers, to date, there is no evidence of direct correlation between high salt diet and human cancers [37].…”

Section: Discussionmentioning

confidence: 99%

Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation

et al. 2017

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Chronic inflammation is a well-known precursor for cancer development and proliferation. We have recently demonstrated that high salt (NaCl) synergizes with sub-effective interleukin (IL)-17 to induce breast cancer cell proliferation. However, the exact molecular mechanisms mediating this effect are unclear. In our current study, we adopted a phosphoproteomic-based approach to identify salt modulated kinase-proteome specific molecular targets. The phosphoprotemics based binary comparison between heavy labelled MCF-7 cells treated with high salt (Δ0.05 M NaCl) and light labelled MCF-7 cells cultured under basal conditions demonstrated an enhanced phosphorylation of Serine-493 of SIK3 protein. The mRNA transcript and protein expression analysis of SIK3 in MCF-7 cells demonstrated a synergistic enhancement following co-treatment with high salt and sub-effective IL-17 (0.1 ng/mL), as compared to either treatments alone. A similar increase in SIK3 expression was observed in other breast cancer cell lines, MDA-MB-231, BT20, and AU565, while non-malignant breast epithelial cell line, MCF10A, did not induce SIK3 expression under similar conditions. Biochemical studies revealed mTORC2 acted as upstream mediator of SIK3 phosphorylation. Importantly, cell cycle analysis by flow cytometry demonstrated SIK3 induced G0/G1-phase release mediated cell proliferation, while SIK3 silencing abolished this effect. Also, SIK3 induced pro-inflammatory arginine metabolism, as evidenced by upregulation of the enzymes iNOS and ASS-1, along with downregulation of anti-inflammatory enzymes, arginase-1 and ornithine decarboxylase. Furthermore, gelatin zymography analysis has demonstrated that SIK3 induced expression of tumor metastatic CXCR4 through MMP-9 activation. Taken together, our data suggests a critical role of SIK3 in mediating three important hallmarks of cancer namely, cell proliferation, inflammation and metastasis. These studies provide a mechanistic basis for the future utilization of SIK3 as a key drug discovery target to improve breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation

et al. 2017

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“…Primitive populations consuming only the natural sodium in foods (<1 g/d) did not show age‐dependent BP increase with age . Populations showing higher sodium consumption tend to have higher BP levels, hypertension prevalence, and cardiovascular mortality …”

Section: Introductionmentioning

confidence: 93%

“…5,6 Populations showing higher sodium consumption tend to have higher BP levels, hypertension prevalence, and cardiovascular mortality. 7,8 A few studies have highlighted to a possible different response of BP according to salt intake between men and women, with controversial results. For instance, a high salt intake during pregnancy in rats was associated to higher rates of hypertension in male offspring than in female offspring.…”

Section: Introductionmentioning

confidence: 99%

Sex‐specific patterns in the association between salt intake and blood pressure: The ELSA‐Brasil study

Mill

Baldo

Molina

et al. 2019

J of Clinical Hypertension

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Blood pressure (BP) is a strong cardiovascular risk factor, predicting cardiovascular mortality in the general population. High salt consumption is a major contributor of increased BP and hypertension. However, there is a controversy on whether BP response to salt intake would be sex‐specific. Thus, we aimed to verify the changes in BP according to different salt intake in men and women in a large sample of adults. The present analysis refers to 12 813 participants (from 35 to 64 years) with a validated 12‐hour overnight urine collection in which salt intake was estimated. A set of questionnaires, clinical examination, and laboratory tests were carried out during a single visit to one of the six investigation centers involved. Salt intake was 12.9 ± 5.9 g/d in men and 9.3 ± 4.3 g/d in women. BP increases as salt intake increases, regardless of using BP‐lowering medication. The slope of increase in BP elicited by salt intake was significantly higher in women than in men. Thus, the increase in BP by salt intake was stepper in women even after controlling for confounders, regardless of using BP‐lowering medication or being hypertensive. In conclusion, salt intake is elevated in this large sample of Brazilian adults in which only a few participants are compliant with the recommendation. Also, women have a higher responsiveness of BP according to salt intake than men, and it is not associated with age, BP level, or the use of BP‐lowering medication.

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“…Salt intake, a major source of sodium in the general population, is at least two times greater than the recommendation and 10 times greater than what was consumed in the past . A high‐salt diet increases cardiovascular morbidity and mortality, being clearly associated with hypertension .…”

Section: Introductionmentioning

confidence: 99%

“…5 Salt intake, a major source of sodium in the general population, is at least two times greater than the recommendation 6 and 10 times greater than what was consumed in the past. 7 A high-salt diet increases cardiovascular morbidity and mortality, being clearly associated with hypertension. 8 Notwithstanding, genetic factors, such as angiotensinconverting enzyme (ACE) gene polymorphisms, a key element in the renin-angiotensin-aldosterone system, have been associated with hypertension, 9 as well as sodium sensitivity, 10 defined as an increase in blood pressure (BP) in response to a higher sodium intake.…”

mentioning

confidence: 99%

Daily sodium intake influences the relationship between angiotensin‐converting enzyme gene insertion/deletion polymorphism and hypertension in older adults

Freire

Casotti

Ribeiro

et al. 2018

J of Clinical Hypertension

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The angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism has been widely reported as being associated with hypertension; however, most studies do not consider environmental/behavioral factors. This study aimed to investigate the relationship among angiotensin-converting enzyme insertion/deletion gene polymorphism, environmental/behavioral factors, and hypertension in community-dwelling elderly individuals. All community-dwelling older adults from Aiquara, Bahia, Brazil, were invited to take part in this study. After exclusions, 234 elderly participants were submitted to a data collection, which included sociodemographics, lifestyle and health status questionnaires, clinical assessment, and blood withdrawal. From the blood samples, the gene polymorphism was identified through polymerase chain reaction and patients grouped as II or D allele carriers (ID and DD genotypes). Hypertension was defined by self-report of the condition and confirmed by antihypertensive drug treatment. Chi-square test was used to identify differences in the proportions distributed between groups of each dependent variable (ie, genotype, diagnosis of hypertension, and blood pressure state from medicated patients with hypertension). The prevalence of hypertension was 59.3% and was associated with diabetes mellitus and obesity, but not with angiotensin-converting enzyme insertion/deletion gene polymorphism. However, carriers of the II genotype, a salt-sensitivity genotype, exhibited a significantly greater estimated sodium intake. In addition, among medicated elderly patients with hypertension, II genotype carriers exhibited poor blood pressure control, despite similar antihypertensive drug treatment in D allele carriers, while exhibiting a greater estimated sodium intake. Our results provide new evidence regarding the interaction of genetic and environmental/behavioral factors in the genesis of hypertension among elderly patients, as well as in blood pressure control in medicated elderly patients with hypertension.

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High salt intake as a multifaceted cardiovascular disease: new support from cellular and molecular evidence

Cited by 33 publications

References 144 publications

Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation

Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation

Sex‐specific patterns in the association between salt intake and blood pressure: The ELSA‐Brasil study

Daily sodium intake influences the relationship between angiotensin‐converting enzyme gene insertion/deletion polymorphism and hypertension in older adults

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