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Genetic basis of cerebrovascular accidents associated with hypertension
1Dipartimento di Patologia e Medicina Sperimentale, Università degli Studi La Sapienza, Roma. speranza.rubattu@neuromed.it
Insights
Stroke is a complex trait influenced by genetics, not just hypertension. Research in stroke-prone rats identified the atrial natriuretic peptide gene as a key human stroke determinant.
Area of Science:
- Cardiovascular Diseases
- Genetics
- Neurology
Background:
- Stroke is a major cause of death and disability globally.
- Stroke is increasingly recognized as a complex trait, influenced by genetic and environmental interactions.
- Identifying human stroke genetics is challenging due to population heterogeneity and confounding factors.
Purpose of the Study:
- To review a strategy for identifying genetic stroke determinants using an animal model.
- To highlight the role of the stroke-prone spontaneously hypertensive rat in genetic stroke research.
- To present findings on the atrial natriuretic peptide gene's role in stroke.
Main Methods:
- Utilized the stroke-prone spontaneously hypertensive rat as an inbred animal model for genetic dissection of cerebrovascular disease.
- Conducted genetic analysis of stroke in this rat model.
- Investigated the link between specific genes and stroke susceptibility.
Main Results:
- Stroke-prone spontaneously hypertensive rat studies confirmed stroke as a genetically determined complex trait.
- Blood pressure and diet were found to play a permissive role, not primary causative roles.
- The gene encoding atrial natriuretic peptide was identified as a significant genetic determinant of stroke in both rats and humans.
Conclusions:
- The genetic basis of stroke is complex and involves multiple factors.
- The atrial natriuretic peptide gene is a validated genetic determinant of human stroke.
- Identifying genetic factors is crucial for developing targeted preventive and therapeutic strategies for cerebrovascular accidents.
Abstract:
Among hypertension-associated cardiovascular diseases, stroke represents one of the most common disorders. In fact, it significantly affects mortality and morbidity rates of all industrialized countries. Only recently, stroke has been considered as a complex trait and not as a mere consequence of hypertension. Indeed, it appears to be the result of an interaction among several genetic and environmental factors. The identification of the genetic determinants of stroke is a difficult task in humans, due to the genetic heterogeneity of human populations and the confounding presence of other risk factors. Thus, an experimental approach, through the use of a highly inbred animal model for stroke, offers a valuable alternative and additional support for a genetic dissection of cerebrovascular disease. In fact, the genetic analysis of stroke in the animal model of the stroke-prone spontaneously hypertensive rat provided clear evidence that stroke is a genetically determined complex trait, and that factors such as blood pressure and diet only play a permissive role. Finally, by using the experimental approach, we established that the gene encoding atrial natriuretic peptide, significantly linked to cerebrovascular disease in rats, is a genetic determinant of stroke in humans. The identification of the genetic basis of stroke represents an important step towards the institution of targeted preventive and therapeutic approaches to reduce the risks of cerebrovascular accidents. This article reviews the background, the experimental approach and the outcome of a strategy based on the use of the stroke-prone spontaneously hypertensive rat model, which aims at identifying the genetic basis of stroke.