Microvascular Genesis of Diseases: From Hypothesis to Theory

Despite progress in understanding the molecular mechanisms of diseases, the dominant paradigm in explaining pathogenesis remains the concept of a pathogen’s direct damaging effect on parenchymal cells. Based on years of research, the authors of this article propose a revision of traditional views on disease pathogenesis. We emphasize the pivotal role of the microvasculature. Existing morphological studies provide insufficient insight into the role of these structures in the development of the pathological process. We conducted a search in international databases to find literary sources current as of December 2025. As an evidence base for the presented concept, we used the results of our own studies published from 1989 to the present. Data from the literature on non-infectious diseases are also separately presented. Our novel data from investigation of infectious and non-infectious diseases demonstrate that even in the initial stages of a pathological process, the microvessels of organs become the primary target of damage. The cascade of pronounced changes in parenchymal cells triggered by this initial event determines the development of the disease. The work examines the cellular and molecular aspects of the interaction between microvessels, pathogens, and the surrounding tissue. The proposed concept provides an objective and fundamentally new explanation for known facts. An important contribution of this concept is its potential to reveal promising directions for further research and for developing innovative approaches to disease therapy.