Most arteriovenous malformations (AVMs) in the stomach trace back to a developmental error before birth, where arteries and veins form direct, abnormal connections instead of linking through a normal capillary network. That said, the picture is more layered than a single cause. Inherited gene mutations, chronic changes in blood-flow pressure, and low-oxygen conditions in the stomach wall can all create or worsen these tangled vessels, sometimes decades after the initial miswiring takes place.
The Embryonic Origin
During fetal development, the primitive vascular system in the gut wall is supposed to gradually separate into distinct arteries, capillaries, and veins. When that process stalls or goes wrong in one spot, a persistent, direct channel between an artery and a vein can remain. This is the classic definition of a congenital AVM: an abnormal artery-to-vein connection that results from embryonic failure in the vascular development of the affected region.
1International Journal of Case Reports and Images. Upper gastrointestinal bleeding revealing a gastric arteriovenous malformation emerging from the splenic arteryBecause they form so early, many gastric AVMs can sit silently for years. The vessels grow along with the rest of the stomach, and the malformation may not cause symptoms until something tips the balance: aging, increased blood pressure in the portal system, or mechanical injury to the overlying mucosa. This helps explain why people are often diagnosed in middle age even though the malformation has technically been present since before birth.
Pathology studies of surgically removed vascular malformations from the gastrointestinal tract show features you would not find in normal stomach tissue. Shunt vessels, tiny wall outgrowths called tufts, and veins whose walls have thickened to resemble arteries (“arterialized veins”) are all more common in true vascular malformations than in other vascular tumors like hemangiomas. Abnormal vessels extending into the mucosal lining, the innermost layer of the stomach, appear almost exclusively in malformations rather than in benign vascular tumors.
2PubMed Central. Vascular malformations and hemangiolymphangiomas of the gastrointestinal tract: morphological features and clinical impactGenetic Conditions That Set the Stage
Some people carry gene mutations that make AVMs far more likely throughout the body, including the stomach. The best-studied example is hereditary hemorrhagic telangiectasia (HHT), an inherited condition that affects roughly 1 in 5,000 to 8,000 people worldwide. HHT comes in two main forms. Type 1 is caused by mutations in the ENG gene on chromosome 9, which encodes a protein called endoglin. Type 2 results from mutations in the ACVRL1 gene on chromosome 12, which encodes a receptor called ALK1. Together, mutations in these two genes account for most diagnosed cases.
3Journal of Thrombosis and Haemostasis. Hereditary hemorrhagic telangiectasia: from molecular biology to patient careBoth endoglin and ALK1 belong to a signaling pathway that helps blood vessels maintain their structural integrity. When one copy of either gene is defective, the body produces less of the corresponding protein than it needs. That reduction alone is usually not enough to cause visible lesions everywhere. Researchers believe a “second hit” is required: something like tissue injury, infection, or low oxygen in a particular stretch of tissue. When that local insult happens in a vessel that is already running low on endoglin or ALK1, the vessel cannot recruit smooth muscle cells properly or regulate the growth of its inner lining. The result is a fragile, malformed connection between artery and vein.
4Haematologica. Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist’s perspectiveHHT is the most common genetic driver, but it is not the only one. PTEN hamartoma tumor syndrome, caused by mutations in the PTEN gene, has been linked to visceral vascular anomalies including high-flow gastrointestinal AVMs. A reported case involved a complex, high-flow gastrointestinal AVM alongside chronic clotting in the portal and mesenteric veins, and genetic testing confirmed PTEN hamartoma tumor syndrome as the underlying condition.
5PubMed Central. Complex Management of High-Flow Gastrointestinal Arteriovenous Malformation With Chronic Portomesenteric Thrombosis in PTEN Hamartoma Tumor SyndromePortal Hypertension and Changes in Stomach Blood Flow
Not every vascular abnormality in the stomach wall began in the womb. Chronic liver disease and the portal hypertension it produces can remodel the stomach’s blood supply in ways that mimic or aggravate malformations. Portal hypertensive gastropathy (PHG) occurs when increased resistance to blood flow through the liver forces extra blood through the stomach’s vessels. The result is a hyperdynamic circulation: total blood flow to the stomach goes up, but paradoxically, flow to the delicate mucosal surface often goes down.
6PubMed Central. Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapyThat mismatch matters. When the deeper muscular and serosal layers of the stomach wall hog more of the blood supply, the surface lining becomes vulnerable to erosion and abnormal vessel dilation. Over time, the constant elevated pressure can open up or enlarge arteriovenous channels that, under normal pressure, would stay small and clinically silent. PHG develops as a complication of both cirrhotic and non-cirrhotic forms of portal hypertension, and the degree of portal pressure appears to be the key factor in whether the gastropathy develops at all.
7PubMed. Portal hypertensive gastropathy: a reviewThe distinction between a “true” congenital AVM and portal-hypertension-driven vascular changes can be tricky even for specialists. In practice, a patient with cirrhosis who presents with a bleeding vascular lesion in the stomach may have a congenital malformation that was unmasked by rising portal pressures, or a lesion that formed entirely because of those pressures. The clinical management is often similar, but the underlying cause shapes whether the problem is likely to recur after treatment.
Low Oxygen and Molecular Signaling
At the molecular level, one of the strongest drivers of abnormal vessel formation in the gut is hypoxia, or low tissue oxygen. When cells in the stomach wall sense that oxygen levels have dropped, they ramp up production of proteins called hypoxia-inducible factors (HIF-1α and HIF-2α). These proteins act as master switches, turning on genes that promote the growth of new blood vessels. In tissue samples from gastrointestinal vascular malformations, HIF-1α and HIF-2α are overactive, and they drive up the production of VEGF, a potent growth signal that pushes endothelial cells to form new tubes. The same pathway also boosts molecules called Notch1, Ang2, and DLL4, all of which enhance vessel-forming behavior in endothelial cells.
8PubMed. Thalidomide-induced angiopoietin 2, Notch1 and Dll4 downregulation under hypoxic condition in tissues with gastrointestinal vascular malformation and human umbilical vein endothelial cellsLaboratory experiments have confirmed this picture. When endothelial cells are placed under low-oxygen conditions, the expression of Ang2, Notch1, and DLL4 all goes up, and the cells form more abundant tubes with larger diameters. In malformation tissue compared to adjacent normal stomach lining, these same proteins show strong activity in the walls and nuclei of cells, whereas normal mucosa shows little to no activity.
8PubMed. Thalidomide-induced angiopoietin 2, Notch1 and Dll4 downregulation under hypoxic condition in tissues with gastrointestinal vascular malformation and human umbilical vein endothelial cellsThis matters practically because the hypoxia pathway is a potential treatment target. The drug thalidomide, for instance, has been studied precisely because it can suppress some of these angiogenic signals. Understanding that low oxygen is not just a bystander but an active promoter of abnormal vessels helps explain why AVMs can grow or bleed more aggressively in settings where stomach-wall oxygenation is compromised, whether from portal hypertension, chronic anemia, or heart failure.
Mechanical Stress and the Caliber Persistent Artery
The stomach is a mechanically busy organ. It expands and contracts with every meal, and its mucosal lining is constantly exposed to acid and digestive enzymes. Physical forces influence how blood flows through the stomach wall. During intestinal contraction and distension, blood flow increases to the muscular layers while the mucosal-submucosal layer sees no corresponding boost.
9PubMed. Motility and blood flow distribution within the wall of the gastrointestinal tractThat asymmetric flow pattern, repeated thousands of times a day, means the mucosa often operates on the margins of adequate blood supply. In areas where an artery is already abnormally large or positioned unusually close to the surface, mechanical stress can erode the overlying tissue and expose the vessel. This is the mechanism behind a Dieulafoy lesion, sometimes called a “caliber persistent artery.” In these cases, a submucosal artery that is normal in structure but abnormally large for its location stays the same diameter all the way to the mucosal surface instead of tapering down as it normally would. A comparative study of these arteries found that their walls are structurally normal and their diameter is appropriate for the submucosal layer. The problem is that at the point where the artery meets the innermost mucosal lining, it is far too large, creating a vulnerable spot where erosion of even a tiny amount of overlying tissue can trigger massive bleeding.
10PubMed Central. The caliber persistent artery of the stomach: a unifying approach to gastric aneurysm, Dieulafoy’s lesion, and submucosal arterial malformationDieulafoy lesions are not AVMs in the strict sense, since they lack the artery-to-vein shunting, but they are frequently grouped with AVMs in clinical practice because they present the same way: sudden, severe gastrointestinal bleeding from an abnormal vessel. The distinction matters more to pathologists than to the person in the emergency department, where the immediate priority is stopping the hemorrhage. Still, knowing that a Dieulafoy lesion is an anatomical quirk of vessel size rather than a true malformation changes what you expect going forward: a Dieulafoy lesion is unlikely to recur after treatment, while a true AVM, especially one with a genetic driver, may form new lesions over time.
Heyde Syndrome and Mechanical Heart Devices
One of the more surprising contributors to gastrointestinal AVM bleeding is aortic stenosis, the narrowing of the heart’s aortic valve. The connection is known as Heyde syndrome. When blood is forced through a narrowed valve, the shear stress unfolds a large blood-clotting protein called von Willebrand factor, exposing it to an enzyme that chops it into smaller, less effective fragments. The result is an acquired clotting deficiency that makes bleeding from existing AVMs far worse.
11Ochsner Journal. Heyde Syndrome Complicated by a Dieulafoy LesionWhether the valve disease also promotes the formation of new AVMs, or merely reveals ones that were already present, remains debated. A large study comparing patients with gastrointestinal AVMs to the general population found no significant differences in average age or sex distribution but did note a higher proportion of Black patients in the AVM group.
12JAMA Internal Medicine. Increased Prevalence of Aortic Stenosis in Patients With Arteriovenous Malformations of the Gastrointestinal Tract in Heyde SyndromeA similar problem has emerged in patients with continuous-flow left ventricular assist devices (LVADs), the mechanical pumps implanted in people with advanced heart failure. These devices produce the same kind of non-pulsatile, high-shear blood flow that damages von Willebrand factor. In a study of patients supported by one widely used LVAD model, AVMs were identified as the bleeding source in about a third of those who developed gastrointestinal hemorrhage. The average age of those AVM patients was in the early sixties, significantly older than the broader population of patients receiving the same device.
13The Journal of Heart and Lung Transplantation. Gastrointestinal Bleeding From Arteriovenous Malformations in Patients Supported by Continuous-Flow Left Ventricular Assist DevicesThese findings suggest that chronic high-shear flow does not just unmask latent AVMs but may actively enlarge or destabilize them. The gut vasculature of an older adult with reduced pulsatile flow and degraded clotting proteins is a very different environment from that of a younger person with normal cardiac output. It is a useful reminder that the “cause” of a gastric AVM is often a layered interaction between a structural predisposition and a hemodynamic insult that arrives years or decades later.
Who Gets Gastric AVMs
Gastric AVMs are uncommon. Digestive-tract AVMs in general account for only about one to two percent of upper gastrointestinal bleeding episodes. Within that small group, the colon, particularly the cecum and ascending colon, is the most frequent site. The stomach is rarer still. Literature reviews place the average age at diagnosis around 56, with a slight predominance of male patients.
14Gastroenterology & Hepatology: Open Access. A rare cause of upper gastrointestinal bleeding in the elderly: gastric arteriovenous malformationThe rarity creates a diagnostic challenge. A gastric AVM may bleed intermittently and then stop on its own, leading to repeated episodes of anemia or dark stools that resist straightforward explanation. Standard upper endoscopy can miss small lesions, especially if they are not actively bleeding at the time of the exam. Many are ultimately found only after repeat procedures or advanced imaging that specifically looks for vascular abnormalities. The low prevalence also means that no large, controlled trials exist to define optimal management. Treatment decisions, whether endoscopic therapy, angiographic embolization, or surgery, tend to be guided by case series and expert opinion rather than randomized evidence.
Why Degenerative Changes in Older Adults Matter
Beyond genetics and portal hypertension, the aging stomach wall itself may contribute to AVM formation or enlargement. As the gastric mucosa thins and the submucosal tissue loses elasticity with age, vessels that were previously well supported by surrounding tissue can become dilated and tortuous. Degenerative changes in the digestive tract wall have been implicated as a contributor to gastric AVMs in older patients, though the precise mechanism has not been fully mapped out.
14Gastroenterology & Hepatology: Open Access. A rare cause of upper gastrointestinal bleeding in the elderly: gastric arteriovenous malformationThis “wear and tear” hypothesis fits the epidemiological pattern. If congenital AVMs were the whole story, you would expect diagnoses to cluster in childhood or young adulthood, when other congenital vascular anomalies usually present. Instead, the average age at diagnosis is well into middle age, and the bleeding that triggers the diagnosis often coincides with other conditions common in older adults: atherosclerosis, hypertension, chronic kidney disease, or anticoagulant use. The aging vessel wall, already operating with less structural support, is more susceptible to the kind of localized hemodynamic stress that can open up or worsen a low-grade arteriovenous connection.
For clinicians, this means that a gastric AVM in a 70-year-old is not necessarily an identical entity to one found incidentally in a 25-year-old with HHT. The former may be largely degenerative, amenable to a one-time endoscopic treatment, and unlikely to recur. The latter may be a marker of a systemic genetic condition that will produce new lesions over time and calls for ongoing surveillance. Understanding which mechanism is dominant in a given patient changes both the treatment plan and the follow-up strategy.