Lactobacillus plantarum 299v administration prevents high-sodium diet-induced glycocalyx degradation and arterial dysfunction
Authors: Zheng Xiangyu , Berg Sen Jennifer , Li Zhuoxin , Cofran Kathryn , Sabouri Mostafa , Bernardo Joseph , Machin Daniel 
Published: May 2024

A central feature of cardiovascular disease (CVD) is arterial dysfunction (i.e., elevated systolic blood pressure [BP], aortic stiffening, and endothelial dysfunction), which may be initiated by a degraded endothelial glycocalyx. The glycocalyx is a negatively charged structure bound to the vascular endothelium that appears to play a critical role in cardiovascular health, particularly by buffering sodium in blood, although excessive sodium degrades the glycocalyx. In the United States, a high-sodium (HS) diet is consumed by ~90% of the population with average sodium intake ~2.3x greater than recommended by the American Heart Association. We have previously shown that HS diet induces glycocalyx degradation and arterial dysfunction in outbred, genetically diverse UM-HET3 mice. Others have shown that HS diet lowers Lactobacillus abundance in mouse gut microbiome. However, it is unknown whether maintaining Lactobacillus would prevent HS diet-induced glycocalyx degradation and arterial dysfunction. To test this concept, male and female UM-HET3 mice (n=21-35/group) were randomized into a low-sodium (LS) diet (1% NaCl), HS diet (4% NaCl), or HS diet with Lactobacillus plantarum 299v (Lp299v) administration (60 million CFU/ml in drinking water) for 12 weeks. Glycocalyx barrier function was determined by assessing perfused boundary region (PBR), which represents red blood cell penetration into the glycocalyx. At week 12, we observed higher PBR in HS mice (2.36±0.04 μm) compared to LS and HS+Lp299v mice (2.09±0.03 and 2.20±0.04 μm, respectively; p<0.05), indicating a worse glycocalyx barrier function in HS mice. PBR was similar between LS and HS+Lp299v mice (P>0.05), indicating a preserved glycocalyx barrier function in HS+Lp299v mice. Systolic BP was higher in HS (127±1 mmHg) compared to LS and HS+Lp299v mice (113±1 and 118±1 mmHg, respectively; p<0.05). Aortic stiffness, determined by aortic pulse wave velocity (PWV), was also higher in HS (345±5 cm/s) compared to LS and HS+Lp299v mice (268±5 and 300±3 cm/s, respectively; p<0.05). However, systolic BP and aortic PWV were higher in HS+Lp299v compared to LS mice (p<0.05). Ex vivo endothelial function, determined by the maximal vasodilatory response to acetylcholine in the carotid artery, was lower in HS (83.9±1.3%) compared to LS and HS+Lp299v mice (89.8±1.3 and 90.1±1.0%, respectively; p<0.05). Endothelial function was similar between LS and HS+Lp299v mice (P>0.05). In summary, Lp299v administration prevents HS diet-induced glycocalyx degradation and endothelial dysfunction, while mitigating HS diet-induced elevations in systolic BP and aortic stiffness. These findings suggest that Lp299v administration may be a novel strategy to lower the risk of CVD in humans that consume a HS diet. This study was funded in part by a grant from the National Institutes of Health (R00 AT010017). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.