# Microvascular Genesis of Diseases: From Hypothesis to Theory

**Authors:** Ruslan A. Nasyrov, Veronika A. Galichina, Anna O. Drobintseva, Daria V. Tonkonog, Elena Yu. Kalinina, Alexandra A. Agafonnikova

PMC · DOI: 10.3390/life16020314 · Life · 2026-02-11

## TL;DR

This paper proposes a new theory that microvascular damage is the starting point for many diseases, challenging traditional views focused on direct cell damage by pathogens.

## Contribution

The paper introduces a novel theoretical framework emphasizing microvascular damage as the initial trigger in disease pathogenesis.

## Key findings

- Microvessels are the primary target of damage in both infectious and non-infectious diseases.
- Initial microvascular injury leads to subsequent parenchymal cell changes that drive disease progression.
- The concept offers a new perspective for future research and therapeutic strategies.

## Abstract

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.

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CALB2 (calbindin 2) [NCBI Gene 794] {aka CAB29, CAL2, CR}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, THBD (thrombomodulin) [NCBI Gene 7056] {aka AHUS6, BDCA-3, BDCA3, CD141, THPH12, THRM}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}
- **Diseases:** chronic fatigue (MESH:D015673), Cryptococcosis of the (MESH:D003453), LS (MESH:D018459), ischemia (MESH:D007511), hypoxia (MESH:D000860), CMV (MESH:D003586), Hypoxic (MESH:D002534), Hirschsprung's Disease (MESH:D006627), obesity (MESH:D009765), hemorrhage (MESH:D006470), atrophic foci (MESH:C565785), multi-organ failure (MESH:D009102), myocardial lesion (MESH:D009059), sclerosis (MESH:D012598), non-infectious diseases (MESH:D000073296), retinopathy (MESH:D058437), Haemophilus Influenzae Infection (MESH:D006192), stroke (MESH:D020521), hypercoagulability (MESH:D019851), Cryptococcal Infection of (MESH:D016919), Diabetic microangiopathy (MESH:D003925), cardiomyopathy (MESH:D009202), ischemic (MESH:D002545), endothelial dysfunction (MESH:D014652), DM (MESH:D003920), ischemic necroses (MESH:D010020), Alzheimer's disease (MESH:D000544), atrophy (MESH:D001284), edema (MESH:D004487), dementia with Lewy bodies (MESH:D020961), ischemic necrosis (MESH:D005271), angina (MESH:D000787), hyperglycemia (MESH:D006943), cerebral hypoperfusion (MESH:D002547), inflammation (MESH:D007249), Neurodegenerative Diseases (MESH:D019636), injury to (MESH:D014947), CMD (MESH:D003327), INOCA (MESH:D000088442), idiopathic Parkinson's disease (MESH:D010300), dyslipidemia (MESH:D050171), Myocardial alterations (MESH:D004408), necrosis (MESH:D009336), fungal neuroinfection (MESH:D009181), neuronal destruction (MESH:D008105), frontotemporal dementia (MESH:D057180), -infectious diseases (MESH:D003141), Long COVID (MESH:D000094024), Haemophilus influenzae meningitis (MESH:D008583), herpes (MESH:C536395), Dermal sclerosis (MESH:D016136), neuropathy (MESH:D009422), DIC (MESH:D004211), cognitive dysfunction (MESH:D003072), kidney diseases (MESH:D007674), Infarction (MESH:D007238), spontaneous abortions (MESH:D000022), heart failure (MESH:D006333), type 1 and type 2 DM (MESH:D003924), neuronal (MESH:D009410)
- **Chemicals:** Toluidine blue (MESH:D014048), ethanol (MESH:D000431), Tocilizumab (MESH:C502936), oxygen (MESH:D010100), glucose (MESH:D005947), H&amp;E (MESH:D006371), Cryptococcal capsular antigen (-), Hematoxylin (MESH:D006416), Diquafosol (MESH:C403315)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], herpesvirus [taxon 39059], Mus musculus (house mouse, species) [taxon 10090], Cryptococcus (genus) [taxon 79213], Homo sapiens (human, species) [taxon 9606], Haemophilus influenzae (species) [taxon 727]

## Full text

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## Figures

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## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942583/full.md

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Source: https://tomesphere.com/paper/PMC12942583