Angiogenic Factors in Cardiovascular and Renal Health

Angiogenic factors are central regulators of blood vessel formation, maintenance and repair, with broad implications for both heart and kidney function. Vascular endothelial growth factor (VEGF) family members, notably placental growth factor (PlGF) and its receptor fms-like tyrosine kinase-1 (Flt-1), govern endothelial survival, permeability and interaction with perivascular cells. A delicate balance between pro-angiogenic signals and their soluble decoys, such as soluble Flt-1 (sFlt-1), underpins vascular homeostasis. Dysregulation of this balance contributes to endothelial dysfunction, hypertension, atherosclerosis and the progression of chronic kidney disease. In diabetes and inflammatory states, altered expression or genetic variation in angiogenic mediators further exacerbates vascular injury. Understanding the mechanisms that control angiogenic factor bioavailability and signalling has yielded biomarkers for disease risk stratification and unveiled targets for novel therapies aimed at restoring vascular integrity in cardiovascular and renal pathologies.

Research from Nature Portfolio

Recent studies have illuminated two complementary aspects of PlGF regulation. First, endothelial cells exposed to high glucose exhibit up-regulation of PlGF through inhibition of the PI3K/Akt pathway and activation of the transcription factor FOXO1. This mechanism links hyperglycaemia directly to pro-inflammatory angiogenic signalling in diabetic vascular complications, suggesting that modulation of the PI3K/Akt/FOXO1 axis could restore angiogenic balance and prevent endothelial injury.

Second, population-based genetic analysis has identified common variants in genes encoding key components of the PlGF signalling network. A genome-wide association approach revealed a major locus at the co-receptor neuropilin-1 (NRP1) and suggestive signals near the primary receptor gene FLT1 and RAPGEF5. Pathway investigations further underscore the interplay between angiogenic and immune pathways in controlling PlGF levels, providing a genetic framework for individual susceptibility to angiogenesis-related diseases.

Angiogenic Factors in Cardiovascular and Renal Health publication trend

The graph below shows the total number of articles in angiogenic factors in cardiovascular and renal health across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: The process of new blood vessel formation from pre-existing vessels.

Vascular endothelial growth factor (VEGF): A family of signalling proteins that promote endothelial cell proliferation, migration and survival.

Placental growth factor (PlGF): A VEGF family member involved in pathological and reparative angiogenesis, especially under stress or injury.

Soluble Fms-like tyrosine kinase-1 (sFlt-1): A circulating decoy receptor that binds VEGF and PlGF, inhibiting their actions and altering vascular permeability.

Endothelial dysfunction: Impaired function of the vascular endothelium characterised by reduced vasodilation, inflammation and pro-thrombotic changes.

References

1. Hyperglycaemia up-regulates placental growth factor (PlGF) expression and secretion in endothelial cells via suppression of PI3 kinase-Akt signalling and activation of FOXO1. Scientific Reports (2021).
2. Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity. Scientific Reports (2021).
3. The Soluble Fms-like Tyrosine Kinase-1 Contributes to Structural and Functional Changes in Endothelial Cells in Chronic Kidney Disease. International Journal of Molecular Sciences (2022).
4. The Importance of Inflammatory and Angiogenic Markers in the Evaluation of Early Cardiovascular Disease Risk in Women with Hypertensive Disorders of Pregnancy. Journal of Cardiovascular Development and Disease (2023).