PIEZO1 mediates a mechanothrombotic pathway in diabetes

Zhu, Wandi; Guo, Songjun; Homilius, Max; Nsubuga, Cissy; Wright, Shane; Quan, Dajun; Ashmita, KC; Eddy, Samuel S; Victorio, Rachelle A.; Beerens, Manu; Flaumenhaft, Robert; Deo, Rahul C.; MacRae, Calum A.

doi:10.1126/scitranslmed.abk1707

Cited by 39 publications

(37 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Surely, our study detected the improvement of host metabolism, particularly in case of borderline normal biomarkers: the consumption of yoghurt with potential probiotic Inducia decreased the values of blood glucose in overweight middle-age healthy volunteers. A recent study explored hyperglycaemia with increased risk of thrombosis and CVD (Zhu et al, 2022). Our finding thus expresses the possible beneficial value of probiotic Inducia consumption on indices of glycemia.…”

Section: Discussionsupporting

confidence: 65%

Impact of Lactiplantibacillus plantarum Inducia on metabolic and antioxidative response in cholesterol and BMI variable indices: randomised, double-blind, placebo-controlled trials

Štšepetova

Rätsep

Gerulis

et al. 2022

View full text Add to dashboard Cite

Probiotics may have potential in reducing cardiovascular disease (CVD) risk in middle-aged persons with borderline metabolic indices. The ability of potential probiotic Lactiplantibacillus plantarum Inducia to reduce CVD risk factors in persons with variable cholesterol and body mass indices (BMI) was assessed. In two parallel-armed double-blind placebo-controlled interventions (n=136) and (n=104), participants daily received either test yoghurt (Inducia) or placebo yoghurt. BMI, blood pressure, plasma glucose, cholesterol, high-sensitivity C-reactive protein (hs-CRP), oxidative stress and immunological markers were measured. Total counts of lactobacilli and L. plantarum Inducia were evaluated using real-time PCR. Significant reduction of total cholesterol, low density lipoprotein cholesterol (LDL-c) and non-high-density cholesterol occurred in both trials. The change in cholesterol (P=0.023) in persons with normal BMI and borderline cholesterol levels after four weeks of yoghurt consumption was detected. A difference was also found between placebo and test yoghurt groups (P=0.042) in LDL-c with normal BMI. Blood glucose reduction (P=0.01) and antioxidative effect was detected in overweight volunteers of the test yoghurt group. The suppression of oxidised LDL was associated with lowered oxidative stress index and total peroxide concentration values and faecal recovery of Inducia. The Inducia strain expresses antioxidative effect on blood lipids and has anti-glycaemic impact that allow to apply it as dietary probiotic supplement for the management of CVD risks in humans.

show abstract

Section: Discussionsupporting

confidence: 65%

Impact of Lactiplantibacillus plantarum Inducia on metabolic and antioxidative response in cholesterol and BMI variable indices: randomised, double-blind, placebo-controlled trials

Štšepetova

Rätsep

Gerulis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, we report for the first time that retrograde perfusion of the diabetic heart releases significantly higher amounts of Hpa L and Hpa A , an effect that could be ascribed to an increase in Piezo1 expression. Indeed, when whole blood was incubated with HG, the expression of Piezo1 increased, 65 an effect that was also seen when we incubated EC in HG. Even more compelling was the response of these HG‐exposed ECs to LF.…”

Section: Discussionsupporting

confidence: 63%

Flow‐Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes

Lee

Zhai

Shang

et al. 2022

JAHA

View full text Add to dashboard Cite

Background Lipoprotein lipase (LPL)‐derived fatty acid is a major source of energy for cardiac contraction. Synthesized in cardiomyocytes, LPL requires translocation to the vascular lumen for hydrolysis of lipoprotein triglyceride, an action mediated by endothelial cell (EC) release of heparanase. We determined whether flow‐mediated biophysical forces can cause ECs to secrete heparanase and thus regulate cardiac metabolism. Methods and Results Isolated hearts were retrogradely perfused. Confluent rat aortic ECs were exposed to laminar flow using an orbital shaker. Cathepsin L activity was determined using gelatin‐zymography. Diabetes was induced in rats with streptozotocin. Despite the abundance of enzymatically active heparanase in the heart, it was the enzymatically inactive, latent heparanase that was exceptionally responsive to flow‐induced release. EC exposed to orbital rotation exhibited a similar pattern of heparanase secretion, an effect that was reproduced by activation of the mechanosensor, Piezo1. The laminar flow‐mediated release of heparanase from EC required activation of both the purinergic receptor and protein kinase D, a kinase that assists in vesicular transport of proteins. Heparanase influenced cardiac metabolism by increasing cardiomyocyte LPL displacement along with subsequent replenishment. The flow‐induced heparanase secretion was augmented following diabetes and could explain the increased heparin‐releasable pool of LPL at the coronary lumen in these diabetic hearts. Conclusions ECs sense fluid shear‐stress and communicate this information to subjacent cardiomyocytes with the help of heparanase. This flow‐induced mechanosensing and its dynamic control of cardiac metabolism to generate ATP, using LPL‐derived fatty acid, is exquisitely adapted to respond to disease conditions, like diabetes.

show abstract

“…47 Moreover, a recent study suggested that hyperglycemia activates the mechanosensory ion channel Piezo1 in blood cells and hematopoietic stem cells, leading to thrombosis in T2D. 48 Finally, as discussed below, normalization of the impaired TRL clearance associated with diabetes is sufficient for the prevention of atherosclerosis in severely hyperglycemic mouse models, 43,49,50 demonstrating that lipid abnormalities override any proatherogenic effects of hyperglycemia. Perhaps hyperglycemia exacerbates the effects of other CVD risk factors?…”

Section: Hyperglycemia Is Not Sufficient To Explain the Increased Cvd...mentioning

confidence: 96%

The Remnant Lipoprotein Hypothesis of Diabetes-Associated Cardiovascular Disease

Bornfeldt

2022

ATVB

View full text Add to dashboard Cite

Both type 1 and type 2 diabetes are associated with an increased risk of atherosclerotic cardiovascular disease (CVD). Research based on human-first or bedside-to-bench approaches has provided new insights into likely mechanisms behind this increased risk. Although both forms of diabetes are associated with hyperglycemia, it is becoming increasingly clear that altered lipoprotein metabolism also plays a critical role in predicting CVD risk in people with diabetes. This review examines recent findings indicating that increased levels of circulating remnant lipoproteins could be a missing link between diabetes and CVD. Although CVD risk associated with diabetes is clearly multifactorial in nature, these findings suggest that we should increase efforts in evaluating whether remnant lipoproteins or the proteins that govern their metabolism are biomarkers of incident CVD in people living with diabetes and whether reducing remnant lipoproteins will prevent the increased CVD risk associated with diabetes.

show abstract

PIEZO1 mediates a mechanothrombotic pathway in diabetes

Abstract: Hematopoietic cell selection based on PIEZO1 expression drives thrombosis risk in type 2 diabetes.

Cited by 39 publications

References 60 publications

Impact of Lactiplantibacillus plantarum Inducia on metabolic and antioxidative response in cholesterol and BMI variable indices: randomised, double-blind, placebo-controlled trials

Impact of Lactiplantibacillus plantarum Inducia on metabolic and antioxidative response in cholesterol and BMI variable indices: randomised, double-blind, placebo-controlled trials

Flow‐Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes

The Remnant Lipoprotein Hypothesis of Diabetes-Associated Cardiovascular Disease

Contact Info

Product

Resources

About