Parental Dietary Protein Source and the Role of
            <i>CMKLR1</i>
            in Determining the Severity of Dahl Salt-Sensitive Hypertension

Abais‐Battad, Justine M.; Lund, Hayley; Fehrenbach, Daniel J.; Dasinger, John Henry; Alsheikh, Ammar J.; Mattson, David L.

doi:10.1161/hypertensionaha.118.11994

Cited by 26 publications

(22 citation statements)

References 54 publications

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“…Antagonism of Chemerin1 attenuated the hypertension of the Dahl S rat fed high salt, as well as renal damage. 115 These studies are significant in that they support the activation of a chemerin receptor as mediating the disease.…”

Section: Chemerin Measures In Normal and Humans With Cardiovascular Dmentioning

confidence: 96%

“… 114 In another study, renal chemerin was elevated in a diabetic model, 31 and Chemerin1 was upregulated in renal T cells in casein fed progeny of the Dahl S rat. 115 This latter study used 2-(α-naphthoyl)ethyltrimethylammonium iodide as a Chemerin1 antagonist. Antagonism of Chemerin1 attenuated the hypertension of the Dahl S rat fed high salt, as well as renal damage.…”

Section: Chemerin Measures In Normal and Humans With Cardiovascular Dmentioning

confidence: 99%

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Chemerin as a Driver of Hypertension: A Consideration

Ferland

Mullick

Watts

2020

American Journal of Hypertension

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The protein chemerin (tazarotene-induced gene, TIG2; RARRES2) is a relatively new adipokine. Many studies support that circulating chemerin levels associate strongly and positively with body mass index, visceral fat, and blood pressure. Here, we focus on the specific relationship of chemerin and blood pressure with the goal of understanding whether and how chemerin drives (pathological) changes in blood pressure such that it could be interfered with therapeutically. We dissect the biosynthesis of chemerin and how current antihypertensive medications change chemerin metabolism. This is followed with a review of what is known about where chemerin is synthesized in the body and what chemerin and its receptors can do to the physiological function of organs important to blood pressure determination (e.g., brain, heart, kidneys, blood vessels, adrenal, and sympathetic nervous system). We synthesize from the literature our best understanding of the mechanisms by which chemerin modifies blood pressure, with knowledge that plasma/serum levels of chemerin may be limited in their pathological relevance. This review reveals several gaps in our knowledge of chemerin biology that could be filled by the collective work of protein chemists, biologists, pharmacologists, and clinicians.

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Section: Chemerin Measures In Normal and Humans With Cardiovascular Dmentioning

confidence: 96%

Section: Chemerin Measures In Normal and Humans With Cardiovascular Dmentioning

confidence: 99%

Chemerin as a Driver of Hypertension: A Consideration

Ferland

Mullick

Watts

2020

American Journal of Hypertension

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“…A, PCoA plot of the weighted UniFrac distance matrix demonstrating that FMT from SS/MCW donors significantly shifted the gut microbial community of SS/CRL recipients (PERMANOVA (all) P = .001; Pairwise PERMANOVA: Donor vs FMT P = .006, Donor vs Vehicle P = .004, Vehicle vs FMT P = .029). B, Global differences in relative abundance of identified ASVs in FMT and vehicle-treated rats at Weeks at Weeks 5, 15 While the SS/CRL Vehicle rats could certainly be described as hypertensive, it is important to note that the disease resistant nature of the SS/CRL is what has allowed these rats to survive a 12 week-long high salt challenge. Additionally, there were no significant changes in heart rate between the two groups (375.0 ± 3.4 vs 362.4 ± 10.1 bpm, FMT vs Vehicle, P = .31, data not shown).…”

Section: Ss/mcw Gut Microbiota Into Protected Ss/ Crl Recipient Rats Raises Blood Pressure Increases Renal Damage and Increases Renal T Cmentioning

confidence: 99%

“…[12][13][14][15] More specifically, this effect of the purified vs grain diet has been attributed to the difference in dietary protein source (casein vs wheat gluten), 12 where there is a clear contribution of the adaptive immune system. [13][14][15] Our recent efforts to understand the influence of the non-sodium components of the diet on salt-sensitive hypertension and renal damage have demonstrated that these changes are related to substantial differences in DNA methylation 16 and gene expression 11 in T-lymphocytes which alter the inflammatory phenotype and ultimately disease severity. As a result of the significant immune-mediated dietary effects observed in the Dahl SS rat and the increasing evidence for the role of the gut microbiota in hypertension and immunity, we hypothesized that the gut microbiota compositions of SS/MCW and SS/CRL are driven by these dietary alterations.…”

Section: Introductionmentioning

confidence: 99%

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt‐sensitive hypertension and renal damage

et al. 2021

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Aim:Our previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt-sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt-sensitive hypertension and renal disease. Methods: This study utilized SS rats from the Medical College of Wisconsin (SS/ MCW) maintained on a purified, casein-based diet (0.4% NaCl AIN-76A, Dyets) and from Charles River Laboratories (SS/CRL) fed a whole grain diet (0.75% NaCl 5L79, LabDiet). Faecal 16S rDNA sequencing was used to phenotype the gut microbiota. Directly examining the contribution of the gut microbiota, SS/CRL rats were administered faecal microbiota transfer (FMT) experiments with either SS/MCW stool or vehicle (Vehl) in conjunction with the HS AIN-76A diet. Results: SS/MCW rats exhibit renal damage and inflammation when fed high salt (HS, 4.0% NaCl AIN-76A), which is significantly attenuated in SS/CRL. Gut microbiota phenotyping revealed distinct profiles that correlate with disease severity. SS/MCW FMT worsened the SS/CRL response to HS, evidenced by increased albuminuria (67.4 ± 6.9 vs 113.7 ± 25.0 mg/day, Vehl vs FMT, P = .007), systolic arterial pressure (158.6 ± 5.8 vs 177.8 ± 8.9 mmHg, Vehl vs FMT, P = .09) and renal T-cell infiltration (1.9-fold). Amplicon sequence variant (ASV)-based analysis of faecal 16S rDNA sequencing data revealed taxa that significantly shifted with FMT: Erysipelotrichaceae_2, Parabacteroides gordonii, Streptococcus alactolyticus, Bacteroidales_1, Desulfovibrionaceae_2, Ruminococcus albus. Conclusions: These data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury. K E Y W O R D S diet, faecal microbiota transfer, gut microbiota, hypertension, immune cells 2 of 16 | ABAIS-BATTAD eT Al.

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“…Renal immune cells. Immune cells in the kidney were isolated as previously described (1,2). Briefly, the left kidney was minced and incubated in RPMI-1640 media containing L-glutamine, HEPES, collagenase type IV, and DNase.…”

Section: Immune Cell Isolationmentioning

confidence: 99%

Salt-sensitive increase in macrophages in the kidneys of Dahl SS rats

Fehrenbach

Abais‐Battad

Dasinger

et al. 2019

American Journal of Physiology-Renal Physiology

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Studies of Dahl salt-sensitive (SS) rats have shown that renal CD3+ T cells and ED-1+ macrophages are involved in the development of salt-sensitive hypertension and renal damage. The present study demonstrated that the increase in renal immune cells, which accompanies renal hypertrophy and albuminuria in high-salt diet-fed Dahl SS rats, is absent in Sprague-Dawley and SSBN13 rats that are protected from the SS disease phenotype. Flow cytometric analysis demonstrated that >70% of the immune cells in the SS kidney are M1 macrophages. PCR profiling of renal myeloid cells showed a salt-induced upregulation in 9 of 84 genes related to Toll-like receptor signaling, with notable upregulation of the Toll-like receptor 4/CD14/MD2 complex. Because of the prominent increase in macrophages in the SS kidney, we used liposome-encapsulated clodronate (Clod) to deplete macrophages and assess their contribution to salt-sensitive hypertension and renal damage. Dahl SS animals were administered either Clod-containing liposomes (Clod-Lipo), Clod, or PBS-containing liposomes as a vehicle control. Clod-Lipo treatment depleted circulating and splenic macrophages by ∼50%; however, contrary to our hypothesis, Clod-Lipo-treated animals developed an exacerbated salt-sensitive response with respect to blood pressure and albuminuria, which was accompanied by increased renal T and B cells. Interestingly, those treated with Clod also demonstrated an exacerbated phenotype, but it was less severe than Clod-Lipo-treated animals and independent of changes to the number of renal immune cells. Here, we have shown that renal macrophages in Dahl SS animals sustain a M1 proinflammatory phenotype in response to increased dietary salt and highlighted potential adverse effects of Clod-Lipo macrophage depletion.

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Parental Dietary Protein Source and the Role of CMKLR1 in Determining the Severity of Dahl Salt-Sensitive Hypertension

Cited by 26 publications

References 54 publications

Chemerin as a Driver of Hypertension: A Consideration

Chemerin as a Driver of Hypertension: A Consideration

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt‐sensitive hypertension and renal damage

Salt-sensitive increase in macrophages in the kidneys of Dahl SS rats

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