A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis

Saleem, Mohammad; Barturen‐Larrea, Pierina; Saavedra, Luz; Gómez, José A.

doi:10.3791/61058

Cited by 4 publications

(4 citation statements)

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Section: Methodsmentioning

confidence: 99%

“…The modified Goldblatt 2-kidney-1 clip (2K1C) murine model of renovascular hypertension was established by placing a polyurethane cuff on the right renal artery following a method reported previously with some modifications (29,30).…”

Section: Surgical Procedurementioning

confidence: 99%

“…The modified 2K1C murine model of renovascular hypertension was established by placing a polyurethane cuff on the right renal artery, according to a method previously reported with some modifications (29,30). We used this method because, according to Lorenz et al (29), using conventional, U-designed silver clips induces a low success rate of hypertension (40%-60%) because the clip laterally presses the artery, triggering a few constrictions, and placement of a plastic cuff would result in a constriction in two dimensions (constriction) rather than one (fl attening), as with a metal clip.…”

Section: Surgical Proceduresmentioning

confidence: 99%

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The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis

Saleem¹,

Saavedra-Sánchez²,

Barturen‐Larrea

et al. 2021

Kidney360

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Background: Renal artery stenosis (RAStenosis) or renal artery occlusion is an intractable problem affecting about 6% of people over 65 and up to 40% of the people with coronary or peripheral vascular disease in the Unites States. In RAStenosis, the renal renin angiotensin aldosterone system (RAAS) plays a key role, with renin recognized as the disease driver. Renin is mainly produced in the kidney and in this study, we will determine a new function for the transcription factor Sox6 in the control of renal renin during RAStenosis. Method: We hypothesize that knocking out Sox6 in Ren1d positive cells will protect mice against renovascular hypertension, and kidney injury. To test our hypothesis, we used a new transgenic mouse model the Ren1dcre/Sox6fl/fl (Sox6 KO). In this mouse, Sox6 is knockout in renin expressing cells. We used a modified two kidney one clip (2K1C) Goldblatt mouse model to induce RAStenosis and renovascular hypertension. Blood pressure was measured with tail-cuff method. Renin, prorenin, Sox6, and N-GAL expressions levels were measured with Western blot, in situ hybridization, and immunohistochemistry. Creatinine levels were measured with colorimetric assay. Results: Systolic blood pressure was significantly lower in Sox6 KO two weeks after RAStenosis compared to Sox6 WT (Ren1dcre/Sox6wt/wt). When stenosed kidneys were compared, renin, prorenin, and N-GAL expressions levels in the kidney were lower in Sox6 KO compared to Sox6 WT mice. Furthermore, creatinine clearance was preserved in Sox6 KO compared to Sox6 WT mice. Conclusions: Our data indicate that Sox6 controls renal renin and prorenin expression and as such has a new function in renovascular hypertension induced by RAStenosis. These results point to a novel transcriptional regulatory network controlled by Sox6.

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Section: Methodsmentioning

confidence: 99%

Section: Surgical Procedurementioning

confidence: 99%

Section: Surgical Proceduresmentioning

confidence: 99%

See 1 more Smart Citation

The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis

Saleem¹,

Saavedra-Sánchez²,

Barturen‐Larrea

et al. 2021

Kidney360

Self Cite

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“…This is because compared with other laboratory animals used in hypertension research, mice have larger surface area to body ratio and consume substantial amount of energy solely for sustaining their body temperature. In mice, the thermoneutral A modified 2K1C procedure was reported in which each individual attempt to constrict the renal artery required manual slicing of a small segment of polyurethane tubing of fixed internal diameter (0.30 mm) lengthwise to produce a cuff followed by placing the cuff around the renal artery and manually closing the gap of the cuff with a silk ligature (Lorenz et al, 2011;Au -Saleem et al, 2020), thereby raising the possibility of operator-dependent variations in the internal diameter of cuff. Of note, this procedure is, per se, more sophisticated and consequently requires longer anesthesia time.…”

Section: Biology Open • Accepted Manuscriptmentioning

confidence: 99%

Improved method for surgical induction of chronic hypertension in mice

2022

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Chronic hypertension can be induced in mice by one-kidney one-clip (1K1C) or two-kidney one-clip surgery, transgenic overexpression of angiotensinogen and renin, administration of deoxycorticosterone acetate-salt, supplying Nitro-L-arginine methyl-ester in the drinking water and Angiotensin-II infusion. Although each model has its own pros and cons, selection of a model that mimics human hypertensive disease accurately is essential to ensure rigor and reproducibility in hypertension research. 1K1C mice represent an efficient, budget-friendly, and translationally capable model, however, its use in preclinical research remained largely hindered due to concerns about potential technical complexity, and lack of reported information regarding procedure-related mortality rates. Here, we describe in detail an improved version of the 1K1C surgery in mice which has zero intraoperative mortality and excellent survival rates in a long-term setting and permits the development of stable chronic hypertension and its target organ complications. Key to this outcome is unilateral nephrectomy 1 week after renal artery clipping to decelerate the BP increase which allows the organism to adapt better to the BP rise. The technical and animal welfare improvements presented here may promote the acceptance of the 1K1C model.

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Renomedullary exosomes produce antihypertensive effects in reversible two-kidney one-clip renovascular hypertensive mice

Huang

et al. 2022

Biochemical Pharmacology

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A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis

Cited by 4 publications

References 0 publications

The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis

The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis

Improved method for surgical induction of chronic hypertension in mice

Renomedullary exosomes produce antihypertensive effects in reversible two-kidney one-clip renovascular hypertensive mice

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