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Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...

Hypoxia

Hypoxia

Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...

Development of Blood Vessels

Development of Blood Vessels

The development of the vascular system in a fetus is a complex and intricate process that begins as early as 15 to 16 days post-conception. This process starts outside the embryo, specifically in the mesoderm of the yolk sac, chorion, and connecting stalk. Approximately two days later, the formation of blood vessels occurs within the embryo itself.
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...

Coronary Circulation

Coronary Circulation

The heart, an organ critical to survival, gets nourishment not from the blood it pumps but from a separate circulation system known as coronary circulation. This is the shortest circulation in the body and is responsible for supplying the heart with the nutrients it needs to function effectively.
Coronary circulation begins at the base of the aorta, where two main arteries arise—the left and right coronary arteries. These arteries encircle the heart in the coronary sulcus and supply the...

Mechanism of Angiogenesis

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...

Development of the Heart

Development of the Heart

The development of the human heart, a crucial organ, commences from the mesoderm on the 18th or 19th day after fertilization. This process initiates in the cardiogenic area, a group of mesodermal cells at the embryo's head end, which evolves into elongated strands known as cardiogenic cords. These cords undergo a transformation to form hollow-centered endocardial tubes.
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart tube by...

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Related Experiment Video

Updated: Jun 9, 2026

Analysis of Coronary Vessels in Cleared Embryonic Hearts

Analysis of Coronary Vessels in Cleared Embryonic Hearts

Published on: December 7, 2016

Hypoxia differentially affects coronary vessel formation during heart development.

Sophie Payne¹, Susann Bruche¹, Dorota Szumska¹

¹Institute of Developmental & Regenerative Medicine (IDRM), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.

Cardiovascular Research

|June 7, 2026

Summary

Hypoxia, or low oxygen, stimulates heart vessel growth primarily through endocardial cells, influencing coronary artery formation. This study clarifies the role of hypoxia and VEGFA in heart angiogenesis.

Keywords:

Angiogenesis Coronary vasculature Heart development Hypoxia VEGFA

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Area of Science:

Cardiovascular Biology
Developmental Biology
Molecular Cardiology

Background:

The coronary vessel system is a complex network crucial for heart function.
Hypoxia (low oxygen) is a known driver of angiogenesis (new blood vessel formation).
The precise mechanisms of hypoxia-induced cardiac angiogenesis, particularly involving Vascular Endothelial Growth Factor A (VEGFA), remain unclear.

Purpose of the Study:

To investigate the specific mechanisms by which hypoxia influences coronary vessel growth and development in the heart.
To elucidate the role of VEGFA and associated regulatory pathways in hypoxia-driven cardiac angiogenesis.

Main Methods:

A genetic model was employed to stabilize Hypoxia-Inducible Factor alpha (HIFα), mimicking myocardial hypoxia.
Single-cell RNA sequencing and enhancer:reporter transgenes were used to analyze changes in coronary endothelial cells (ECs).
Investigated activity in different coronary vessel beds and regulatory pathways, including VEGFA-MEF2.

Main Results:

Mimicking hypoxia increased angiogenic gene expression and expanded the VEGFA-MEF2 pathway activity.
Evidence pointed towards increased angiogenic sprouting originating from endocardial cells.
Sprouting from the sinus venosus (SV)-derived plexus showed minimal change; initial arterial EC differentiation was unaffected, but mature arterial formation was delayed.

Conclusions:

Hypoxia directly and specifically promotes endocardial coronary vessel sprouting.
Hypoxia and VEGFA play a role in guiding the coalescence of coronary arteries.
Findings highlight the distinct contributions of different cell sources to cardiac angiogenesis under hypoxic conditions.